ABSTRACT
Mammalian Target of Rapamycin (mTOR) signaling pathway has important roles in the regulation of puberty onset, gonadotropin secretion, follicular development and ovulation. Melatonin (N-acetyl-5-methoxytryptamine) is a lipophilic hormone has multiple functions in regulating the fertility. Recent studies have shown that melatonin affected the number or maturation of follicles in the ovary. The aim of this study was to investigate the effects of melatonin on mTOR expression and quantity of follicle in rat ovary. In the present study, a total of 45 female rats were randomly divided into three groups. Group 1; Control (C), Group 2: Vehicle (V) and Group 3; Melatonin (M). Melatonin was administered intraperitoneally at a dose of 50 mg/kg/day for 30 days in Melatonin group. The effects of Melatonin on the expression of mTOR and downstream components were determined by Western Blot and Reverse Transcriptase PCR analysis. Upon Western Blot and RT-PCR evaluations, we detected higher expression and activation of mTOR, P70S6K, PKCalpha, PCNA and higher numbers of primordial follicles in melatonin group compared with V and C group. In addition to this results, melatonin decreased oxidative stress markers, such as MDA, on the contrary, levels of antioxidative markers, such as CAT and GPx, were increased by melatonin in rat ovary. This study indicated that melatonin may have a significant protective effect on primordial follicles and increase the expression of mTOR and downstream components in rat ovary. Melatonin treatment may have a beneficial effect on fertility.
Subject(s)
Melatonin/pharmacology , Ovarian Follicle/drug effects , Ovary/drug effects , Oxidative Stress/drug effects , Signal Transduction/drug effects , TOR Serine-Threonine Kinases/metabolism , Animals , Antioxidants/administration & dosage , Antioxidants/pharmacology , Blotting, Western , Catalase/metabolism , Female , Gene Expression/drug effects , Glutathione Peroxidase/metabolism , Injections, Intraperitoneal , Malondialdehyde/metabolism , Melatonin/administration & dosage , Ovarian Follicle/metabolism , Ovary/metabolism , Proliferating Cell Nuclear Antigen/metabolism , Protein Kinase C-alpha/genetics , Protein Kinase C-alpha/metabolism , Rats, Wistar , Reverse Transcriptase Polymerase Chain Reaction , Ribosomal Protein S6 Kinases, 70-kDa/genetics , Ribosomal Protein S6 Kinases, 70-kDa/metabolism , Signal Transduction/genetics , Superoxide Dismutase/metabolism , TOR Serine-Threonine Kinases/geneticsABSTRACT
Immunophilins are a family of receptors for immunosuppressive drugs like cyclo-sporin A, FK506, rapamycin and their non-immunosuppressive analogues, which are collectively referred to as immunophilin ligands. The present study aimed to review neuroprotective and neuroregenerative actions of immunophilin ligands on peripheral nerve injuries. The special emphasis was given to well-known immunosuppressive drug FK506. Its historical background, administration routes, dosages, neuroregenerative, neuroprotective actions, therapeutic time window in administration, action mechanism and side effects of FK506 were reviewed.
ABSTRACT
Melatonin has many different roles in the human body, including its importance in circadian rhythms, sleep physiology, mental status, reproduction, tumour development, ageing, and many other physiologic processes. Although there are more than hundreds of studies on effects of melatonin in several tissues, its effects on peripheral nerve has been documented in a limited number of studies. This paper focused to review the available literature in terms of several actions and effects of melatonin (beneficial or toxic effects) on well-known peripheral nerve injury models.
