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1186 Doaa M. Mokhtar et al.


lion cells) that are intimately related to chromaffin cells and innervated by preganglionic fibers to control their secretion. The current results recorded a significant increase in the diameter of ganglion cells, amount of their rER, nerve fibers and nucleus to cytoplasmic ratio in the treated group that are morphological indicators to increase the functional activity of these cells. The present study demonstrated that the melatonin


pheochromocytomas (tumors of chromaffin cells in the adrenal medulla). PMD may regulate exocytosis, it has been proposed that the discharge mechanism implies the forma- tion of vesicles that shuttle back and forth between the granules and the plasma membrane (Dvorak et al., 1996; Dvorak, 1998). We propose that PMD in adrenal chromaffin cells may provide a finely controlled mechanism of cate- cholamine discharge by granule deposits. Indeed, transfer to the cell exterior of a small quantity of secretory material through an outward vesicle flow would allow a subtle modu- lation of hormone release. PMD may be a general degranu- lation pattern in cells involved in paracrine–endocrine secretion (Crivellato et al., 2004). The adrenal medulla always contains perikarya (gang-


stimulation through an increase in cytoplasmic volume, according to Decker & Quay (1982). Benítez-King (2006) demonstrated that melatonin is capable of influencing microfilament, microtubule, and intermediate filaments organization by acting as a cytoskeletal modulator. TCs have been reported in a wide range of tissues, usually in close proximity to smooth muscle, and have been particularly well studied along the digestive tract (Rumessen, 1994), fallopian tube and uterus (Duquette et al., 2005), blood vessels (Li et al., 2014), and seminal vesicles (Mokhtar et al., 2016). Cretoiu et al. (2009) suggested that these cells participate in the exchange of genetic information with immune cells and nerve fibers or for sensing changes in stromal micro- environment. They also may contribute to tissue regenera- tion (Zheng et al., 2012). Moreover, TCs have a role in contractile activity (Carmona et al., 2011) and act as a pacemaker (Sanders et al., 2006) and supporting cells in tissue organization (Rusu et al., 2012). The most striking results in this study were the high


observation of TCs in the adrenal gland of sheep for the first time. The current results agreed with our previous study that melatonin treatment induced an increase in secretory activity of these cells and their contact with blood vessels and nerve fibers (Abd-Elhafeez et al., 2017). Melatonin caused an increase in the length of Tps that may be due to cellular


(MT2) by fibroblasts were recorded by Choi et al. (2011) and this may explain increased activity of fibroblasts after mela- tonin treatment. Moreover, the progenitor stem cells were active in the current study after melatonin treatment and this may due to direct action of melatonin receptors on these cells as well as stem cells express MT1 receptor according to Niles et al. (2004). The most interesting result in the present study is the


the first time in our study. The treated group was characterized by co-existence of the synaptic-like vesicles and electron-dense secretory granules in the SGC cells. Moreover, the synaptic vesicles were observed peripherally in their cytoplasm and this might suggest their release into adjacent tissue spaces. Yokota (1973) suggested that SGC may represent an intermediate position between the chromaffin and sympathetic nerve cells and suggest presence of catecholamines. On the other hand, Eranko & Eranko (1971) have proposed a chemoreceptor function for these cells. The expression of melatonin receptors (MT1) and


treatment induced an increase in the number of nerve fibers, which was supported by findings of Uyanikgil et al. (2017) who proved that melatonin affected the morphological fea- tures of nerve tissue and has a neuroprotective role through involvement in regeneration of peripheral nerves. Moreover, melatonin exerted a positive effect on axon length and development after peripheral nerve stress. It also has positive effects not only on the number and diameter of axon, but also on the thickness of the myelin sheath. The SGCcells are recognized in adrenalmedulla of ram for


expression of TH in chromaffin cells of the adrenal medulla in the melatonin-treated groups compared with the controls. SYP is an integral membrane glycoprotein that has been identified initially in presynaptic vesicles of neurons and of chromaffin cells in the adrenal medulla (Jahn et al., 1985; Wiedenmann & Franke, 1985). Moreover, SYP is expressed in the small vesicle of the neuroendocrine cells (Wiedenmann, 1991). In our study, the SYP expression was restricted to the adrenal medullary cells in both the control and melatonin-treated groups, while no reaction was recor- ded in the adrenal cortex. While in cases of tumors, SYP was expressed in cortex according to Feng et al. (2005) who demonstrated that SYP was exclusively detected in the adrenocortical adenomas, adrenocortical carcinoma, and adrenal metastatic carcinoma, so, this could prove that melatonin treatment did not cause any type of tumors. Several previous studies proved that melatonin has


potent endogenous antioxidant actions. The neuro- degenerative disorders are mainly caused by oxidative damage, so, melatonin has been tested successfully in both in vivo and in vitro models for treatment of Parkinson dis- ease (PD). In addition, melatonin involved in neuroprotec- tion of neurons in PD (Mayo et al., 2005). In conclusion, melatonin elicits a stimulatory action on


the cells of adrenal cortex and medulla. Melatonin may act as a new direction for treatment of adrenal insufficiency and could profitably apply to some neuronal problems. Melatonin may be involved in regulation of many metabolic functions. Future research in this field should be done to ensure the effect of melatonin for therapeutic causes under clinical conditions.


ACKNOWLEDGMENTS


The authors are grateful to Prof. G.A. Lincoln, professor of physiology at MRC, Edinburgh, for his great support in the collection of samples for this experiment, and we extend our acknowledgment to all the technicians of MRC for their


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