Effect of melatonin on ram adrenal gland 1185
Langevad et al., 2014). However, the effects of exogenous melatonin on the adrenal gland at immunohistochemical and ultrastructural level have received little attention. Several suggested hypotheses are concerned with the
mechanism of melatonin at the cellular level. Pandi-Perumal et al. (2008) reported that melatonin receptors mediate changes in intracellular cyclic nucleotides (cyclic adenosine monophosphate, cyclic guanosine monophosphate) and activation of certain protein kinase C subtypes and intracellular steroid hormone receptors. Moreover, Tomás-Zapico & Coto- Montes (2005) added that melatonin stimulates intracellular Ca2+ that plays an important role in a broad array of cellular functions, including the activation of transcription and regulation of various cellular processes. In the present study, melatonin administration was shown to stimulate a variety of cells in the adrenal gland thatwas in accordance with Decker& Quay (1982), who proved that melatonin causes cellular stimulation through an increase in the cytoplasmic, nuclear volume, and the number and area of mitochondria per cell. The conversion of cholesterol to aldosterone
occurs through a series of enzyme-mediated steps in the mitochondria and sER and stored in the lipid droplets (Nussdorfer et al., 1978). The present results revealed hypertrophy in zona glomerulosa with a lamellar pattern of mitochondrial cristae after melatonin treatment, which was in accordance with Rebuffat et al. (1988) who recorded a significant rise in the plasma concentration of aldosterone after melatonin administration in rats. These findings indi- cate that melatonin exerts a strong direct stimulatory action on the growth and steroidogenic capacity of zona glomer- ulosa. Moreover, increased sER profiles and lipid droplets in the cortex in treated group are attributed to increasing cortical hormones followed by increase steroidogenic func- tion. ACTH not only stimulates corticosteroid synthesis, but also maintains adrenocortical cells and increases blood flow through the adrenal gland (Ross et al., 1995). The results indicated that melatonin treatment caused
an increase in the number of lipid droplets in adrenal cortical cells. Recent studies (Jin et al., 2017) reported that melatonin has a role in the regulation of lipid metabolism. They added that melatonin treatment significantly enhanced the number of lipid droplets and upregulated gene expression related to lipogenesis. Moreover, melatonin significantly increased the content of fatty acids, mitochondria, and ATP. In addition, melatonin upregulated mRNA expression levels of lipo- genesis, lipolysis, β-oxidation, and mitochondrial biogenesis- related genes. The presence of intercellular canaliculi between the
adrenal cortical cells that open into the subendothelial spaces, cause a significant increase in the surface of the par- enchymal cells exposed to the extracellular fluid, and the occurrence of coated pits, are thought to be involved in hormone secretory processes (Nussdorfer et al., 1978). The current study supposes that intercellular canaliculi are the site of hormone release or the site at which circulating melatonin (or other adrenocorticotropic factors) obtains access to the plasma membrane receptors. In some images,
sporadic dense granules were seen inside the lumen of intercellular canaliculi supposed exocytosis. Adrenaline synthesis from noradrenaline is stimulated
by the glucocorticoids produced from zona fasciculate of the adrenal cortex (Carrasco-Serrano & Criado, 2004). These hormones reach the adrenal medulla through an extended capillary network. In the secretory granules of chromaffin cells, catecholamines form a storage complex with chromo- granins (glycoprotein), neuropeptides, adenine nucleotides, and Ca+2 (Winkler & Carmichael, 1982). Tyrosine comes from dietary sources or from the hepatic conversion of phenylalanine. It is converted to dihydroxyphenylalanine by TH, and decarboxylated to produce dopamine. The enzymes involved in these steps are localized in the cytosolic com- partment of the cell. Dopamine is transported into neuro- secretory granules for the synthesis of norepinephrine, which is taken back into the cytosol for conversion to epinephrine, which in turn is transported back into secretory granules for storage (Wurtman, 2002). The most striking ultrastructural features of the adrenal
medulla in melatonin-treated group were a package of chromaffin cells by secretory granules and dilatation of intercellular blood sinusoids that indicated a hypersecretory effect of melatonin on chromaffin cells and another direct effect on sinusoids. The adrenal chromaffin cells possess ultrastructural features typical of the peptide/amine- secreting endocrine cells. Chromaffin cells resemble neurons as they associated with synaptic-type nerve endings and receive cholinergic synapses from preganglionic nerve fibers (Lewis & Shute, 1969). On the other hand, activation of preganglionic sympathetic nerves might play a role in inducing adrenal hypertrophy, and enhanced catecholamine synthesis (Schneider et al., 2011). Catecholamine secretion from chromaffin cells has been
used for a long time as a general model to study exocytosis of large dense core secretory granules. However, the mechani- sms regulating secretion are multiple and cell specific (Aunis, 1998). In the present study, exocytosis with active release of secretory granules to blood vessels was well defined in the treated group and less observed in the control group, which may be due to slow rate of secretion. One of the major functions of the membranes of secretory vesicles is the transport of peptides from the Golgi region to the plasma membrane, where secretion by exocytosis occurs. Exocytosis is considered a rapid means of granule content discharge and is therefore well suited for sustaining a quick adaptive reaction. Another mechanism of chromaffin cell secretion was
evident in the treated group referred to as “kiss-and-run” exocytosis, “fuse-pinch-and-linger” exocytosis, and “poro- cytosis” (Ryan, 2003). In this process, the secretory granules would discharge their contents by PMD (Crivellato et al., 2003). PMD is a unique model of cell secretion characterized by the slow release of granule materials without granules opening to the cell exterior. The previous data appear to indicate that PMD plays a profound role in sustaining the chronic high catecholamine levels observed in patients with
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