title: Melatonin replacement restores the circadian behavior in adult rat Leydig cells after pinealectomy.
abstract: Melatonin actions on oscillators in reproductive organs are poorly understood. Here we analyzed melatonin effects on rhythmic expression of clock and steroidogenesis-related genes in adult rat Leydig cells (LCs). The effect of melatonin was tested both in vivo using pinealectomized and melatonin-substituted rats and in vitro on isolated LCs. Data revealed 24-h-rhythmic expression of clock genes (Bmal1, Per1,2,3, Rev-erba,b, Rorb), steroidogenic genes (Star, Cyp11a1, Cyp17a1), and genes of steroidogenic regulators (positive-Nur77, negative-Arr19). Pinealectomy increased 24-h-oscillations of serum testosterone and LC's cAMP levels, expression of Insl3, Per1, Star/StAR, Hsd3b1/2, Nur77, decreased Arr19 and canceled Per2 oscillatory expression pattern. At hypothalamic-pituitary level, pinealectomy increased mesor of Gnrh, Lhb and rhythm robustness of Mntr1a expression. All parameters disturbed were restored by melatonin-replacement. In vitro studies did not confirm direct melatonin effects on neither clock nor steroidogenic genes. Accordingly, melatonin influence 24-h-rhythmic LC-function likely through hypothalamic-pituitary axis and consequently cAMP-signaling in LCs.
authors.affiliation: Department of Biology and Ecology, Faculty of Sciences, University of Novi Sad, Novi Sad, Serbia.
authors.forename: Aleksandar Z
authors.initials: AZ
authors.lastname: Baburski
authors.affiliation: Department of Biology and Ecology, Faculty of Sciences, University of Novi Sad, Novi Sad, Serbia.
authors.forename: Srdjan J
authors.initials: SJ
authors.lastname: Sokanovic
authors.affiliation: Department of Biology and Ecology, Faculty of Sciences, University of Novi Sad, Novi Sad, Serbia.
authors.forename: Marija M
authors.initials: MM
authors.lastname: Janjic
authors.affiliation: Department of Biology and Ecology, Faculty of Sciences, University of Novi Sad, Novi Sad, Serbia.
authors.forename: Natasa J
authors.initials: NJ
authors.lastname: Stojkov-Mimic
authors.affiliation: Department of Biology and Ecology, Faculty of Sciences, University of Novi Sad, Novi Sad, Serbia.
authors.forename: Maja M
authors.initials: MM
authors.lastname: Bjelic
authors.affiliation: Department of Biology and Ecology, Faculty of Sciences, University of Novi Sad, Novi Sad, Serbia.
authors.forename: Silvana A
authors.initials: SA
authors.lastname: Andric
authors.affiliation: Department of Biology and Ecology, Faculty of Sciences, University of Novi Sad, Novi Sad, Serbia. Electronic address: tatjana.kostic@dbe.uns.ac.rs.
authors.forename: Tatjana S
authors.initials: TS
authors.lastname: Kostic
mesh_terms: D000818:Animals; D002940:Circadian Rhythm / Q000187:drug effects*; D056925:Circadian Rhythm Signaling Peptides and Proteins / Q000096:biosynthesis*; D005786:Gene Expression Regulation / Q000187:drug effects*; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism*; D007985:Leydig Cells; D008297:Male; D008550:Melatonin / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D056925:Circadian Rhythm Signaling Peptides and Proteins; D008550:Melatonin
keywords: 24-H rhythm; Clock; Leydig cell; Melatonin; StAR; Steroidogenic genes; cAMP