Melatonin replacement restores the circadian behavior in adult rat Leydig cells after pinealectomy. (15th September 2015)

• Record Type: Journal Article
• Authors: Baburski, Aleksandar Z.; Sokanovic, Srdjan J.; Janjic, Marija M.; Stojkov-Mimic, Natasa J.; Bjelic, Maja M.; Andric, Silvana A.; Kostic, Tatjana S.
• Is Part Of: Molecular and cellular endocrinology. Volume 413(2015)
• Page Start: 26
• Page End: 35
• Publication Date: 2015-09-15
• Subjects: Leydig cell -- Melatonin -- 24-H rhythm -- Clock -- Steroidogenic genes -- cAMP -- StAR; ACTB protein β-actin -- Adcy gene for adenylyl cyclases -- Bmal1 brain-muscle Arnt-like protein 1 -- BSA bovine serum albumin -- cAMP cyclic adenosine monophosphate -- Cga alpha polypeptide of glycoprotein hormones -- Ck1 gene for casein kinase 1 -- Clock/CLOCK gene/protein for circadian locomotor output cycles kaput -- CRE cAMP-responsive element -- Creb/CREB gene/protein for cAMP response element-binding protein -- Cry/CRY gene/protein for cryptochrome -- Cyp11a/CYP11a gene/protein for cytochrome P450 side chain cleavage enzyme -- Cyp17a/CYP17a gene/protein for 17α-hydroxylase/C17-20 lyase -- Dax1/DAX1 gene/protein for dosage-sensitive sex reversal -- DHT dihydrotestosterone -- DMEM/F12 Dulbecco's modified eagle medium -- E4bp4 gene for Nuclear factor interleukin 3 regulated -- Gapdh gene for glyceraldehyde 3-phosphate dehydrogenase -- Hsd17b gene for hydroxysteroid dehydrogenase 17β -- Hsd3b gene for hydroxysteroid dehydrogenase 3β -- Insl3/INSL3 gene/protein for insulin-like 3 -- LCs Leydig cells -- LH luteinizing hormone -- Lhr/LHR gene/protein for luteinizing hormone receptor -- Lhb gene for LH β subunit -- Mntr1a, b/MNTR1a, b gene/protein for melatonin receptor 1 or 2 -- Npas2 gene for Neuronal PAS domain-containing protein 2 -- Nur77 gene for nerve growth factor -- P pinealectomized rats -- P + M pinealectomized rats received melatonin -- Pde cAMP-specific 3′, 5′-cyclic phosphodiesterase -- Per1 period circadian protein 1 -- Per2 period circadian protein 2 -- PKA cAMP dependent protein kinase -- RIA radioimmunoassay -- Rev-erba/b / REV-ERBA/B gene/protein for reverse viral erythroblastis oncogene product alpha/beta -- Ror/ROR retinoid acid related orphan receptor -- RQ-PCR relative quantification polymerase chain reaction -- Sf1 gene for steroidogenic factor 1 -- SP sham pinealectomized rats -- Star/StAR gene/protein for steroidogenic acute regulatory protein -- T testosterone -- ZT Zeitgeber (German: "time giver") time; Endocrinology -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Endocrinology -- Periodicals; Hormones -- Periodicals; Endocrinologie -- Périodiques; Cytology; Endocrinology; Molecular biology; Periodicals; 573.4
• DOI: 10.1016/j.mce.2015.05.039
• Languages: English
• ISSNs: 0303-7207

Abstract

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. Graphical abstract: Highlights: Leydig cells exhibit 24-h rhythmic expression of clock and steroidogenic genes. Melatonin act on GnRH-LH axis and consequently modulate rhythmic LCs physiology. Melatonin shapes 24-h fluctuation of testosterone and cAMP in Leydig cells. Melatonin influences Insl3, StAR, Hsd3b, Nur77, Arr19, Per1, 2 expression amplitude.