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Horm Metab Res 2017; 49(02): 86-94
DOI: 10.1055/s-0042-111012
Endocrine Research
© Georg Thieme Verlag KG Stuttgart · New York

TRH and TRH-Like Peptide Levels Co-Vary with Reproductive and Metabolic Rhythms

E. Pekary
1   Research Service, VA Greater Los Angeles Healthcare System, Los Angeles, USA
2   Center for Ulcer Research and Education, VA Greater Los Angeles Healthcare System, Los Angeles, USA
3   Department of Medicine, University of California, Los Angeles, USA
,
A. Sattin
1   Research Service, VA Greater Los Angeles Healthcare System, Los Angeles, USA
4   Department of Psychiatry, University of California, Los Angeles, USA.
5   Departments of Psychiatry & Biobehavioral Science, University of California, Los Angeles, USA
6   Brain Research Institute, University of California, Los Angeles, USA
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Publikationsverlauf

received 29. Februar 2016

accepted 15. Juni 2016

Publikationsdatum:
19. Juli 2016 (online)

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Abstract

Photoperiod-synchronized rhythms in non-CSN tissues persist in total darkness. Clock genes involved in maintaining regular biorhythms within the suprachiasmatic nucleus (SCN) of the hypothalamus are expressed in extra-CNS tissues and continue periodic expression in vitro. Understanding the details of how the SCN clock is coupled with peripheral clocks is only incompletely understood and may involve a multiplicity of feedback systems. The present study is an extension of our previous work showing that brain levels of TRH (pGlu-His-Pro-NH2) and TRH-like peptides (X-TRH: pGlu-X-Pro-NH2, where “X” can be any amino acid residue) fluctuate throughout the day-night cycle. Male rats were maintained in a stable environment, lights on 6–18 h. TRH and TRH-like peptides in liver, pancreas, testis, prostate, epididymis, and heart were measured at 3, 10, 16, and 22 h. The greatest change in peptide level was a 12-fold increase for TRH in prostate at 16 h relative to the corresponding value at 3 h. The TRH, Tyr-TRH and Phe-TRH levels in liver declined steadily to about 40% of the 3-h values by 22 h. Changes, in the order of decreasing number of significant increases (↑) and/or decreases (↓), were: testis (5↑, 1↓), liver (3↓), epididymis (2↑), prostate (1↑, 1↓) and heart (1↑). Peptide levels in liver and testis correlated with serum leptin and serum corticosterone, respectively, which are potent releasers of these peptides. Testosterone and glucose were also highly correlated. These tripeptides may participate in the regulation of metabolic and reproductive functions, which change during the day-night cycle.

Key words

thyrotropin-releasing hormone - reproduction - metabolism
 

  • References

  • 1 Pekary AE, Stevens SA, Sattin A. Circadian rhythms of TRH-like peptide levels in rat brain. Brain Res 2006; 1125: 67-76
    CrossrefPubMedGoogle Scholar
  • 2 O’Neill RD, Fillenz M. Circadian changes in extracellular ascorbate in rat cortex, accumbens, striatum and hippocampus: correlations with motor activity. Neurosci Lett 1985; 60: 331-336
    CrossrefPubMedGoogle Scholar
  • 3 Pekary AE. Chapter 126. TRH. In: Kastin AJ. (ed.) The Handbook of Biologically Active Peptides. 2nd (ed.). Waltham: Elsevier; 2013: 951-956
    CrossrefGoogle Scholar
  • 4 Fernandez F, Lu D, Ha P, Costacurta P, Chavez R, Heller HC, Ruby NF. Circadian rhythm. Dysrhythmia in the suprachiasmatic nucleus inhibits memory processing. Science 2014; 346: 854-857
    CrossrefPubMedGoogle Scholar
  • 5 LeGates TA, Altimus CM, Wang H, Lee HK, Yang S, Zhao H, Kirkwood A, Weber ET, Hattar S. Aberrant light directly impairs mood and learning through melanopsin-expressing neurons. Nature 2012; 491: 594-598
    CrossrefPubMedGoogle Scholar
  • 6 Bednarova A, Kodrik D, Krishnan N. Nature’s timepiece-molecular coordination and its impact on aging. Int J Mol Sci 2013; 14: 3026-3049
    CrossrefPubMedGoogle Scholar
  • 7 Gale JE, Cox Heather I, Qian J, Block GD, Colwell CS, Matveyenko AV. Disruption of circadian rhythms accelerates development of diabetes through pancreatic beta-cell loss and dysfunction. J Biol Rhythms 2011; 26: 423-433
    CrossrefPubMedGoogle Scholar
  • 8 Mauvoisin D, Wang J, Jouffe C, Martin E, Atger F, Waridel P, Quadroni M, Gachon F, Naef F. Circadian clock-dependent and –independent rhythmic proteomes implement distinct diurnal function in mouse liver. Proc Natl Acad Sci USA 2014; 111: 167-172
    CrossrefPubMedGoogle Scholar
  • 9 Nguyen TT, Mattick JSA, Yang Q, Orman MA, Ierapetritou MG, Berthiaume F, Androulakis IP. Bioinformatics analysis of transcriptional regulation of circadian genes in rat liver. BMC Bioinformatics 2014; 15: 83
    CrossrefPubMedGoogle Scholar
  • 10 Stashi E, Lanz RB, Mao J, Michailidis G, Zhu B, Kettner NM, Putluri N, Reineke EL, Reineke LC, Dasgupta S, Dean A, Stevenson CR, Sivasubramanian N, Sreekumar A, DeMay F, York B, Fu L, O’Malley BW. SRC-2 is an essential coactivator for orchestrating metabolism and circadian rhythm. Cell Rep 2014; 6: 633-645
    CrossrefPubMedGoogle Scholar
  • 11 Cagnacci A, Maxia N, Volpe A. Diurnal variation in sperm quality in human males. Hum Reprod 1999; 14: 106-109
    CrossrefPubMedGoogle Scholar
  • 12 Kus I, Songur A, Ozogul C, Kavakli A, Zararsiz I, Sarsilmaz M. Effects of photoperiod on the ultrastructure of Leydig cells in rat. Arch Androl 2004; 50: 193-200
    PubMedGoogle Scholar
  • 13 Ebling FJ. On the value of seasonal mammals for identifying mechanisms underlying the control of food intake and body weight. Horm Behav 2014; 66: 56-65
    CrossrefPubMedGoogle Scholar
  • 14 Morgan PJ, Ross AW, Mercer JG, Barrett P. Photoperiodic programming of body weight through the neuroendocrine hypothalamus. J Endocrinol 2003; 177: 27-34
    CrossrefPubMedGoogle Scholar
  • 15 Wyse CA, Selman C, Page MM, Coogan AN, Hazlerigg DG. Circadian desynchrony and metabolic dysfunction; did light pollution make us fat?. Med Hypotheses 2011; 77: 1139-1144
    CrossrefPubMedGoogle Scholar
  • 16 Molcan L, Teplan M, Vesela A, Zeman M. The long-term effects of phase advance shifts of photoperiod on cardiovascular parameters as measured by radiotelemetry in rats. Physiol Measurement 2013; 34: 1623-1632
    CrossrefPubMedGoogle Scholar
  • 17 Zeman M, Herichova I. Melatonin and clock genes expression in the cardiovascular system. Front Biosci (Schol Ed) 2013; 5: 743-753
    PubMedGoogle Scholar
  • 18 Edmonds KE, Stetson MH. Effects of age and photoperiod on reproduction and the spleen in the marsh rice rat (Oryzomys palustris). Am J Physiol Regul Integr Comp Physiol 2001; 280: R1249-R1255
    CrossrefPubMedGoogle Scholar
  • 19 Hadley AR, Tran LT, Fagoaga OR, Nehlsen-Cannarella SL, Yellon SM. Sex differences in photoperiod control of antigen-specific primary and secondary humoral immunity in Siberian hamsters. J Neuroimmunol 2002; 128: 39-48
    CrossrefPubMedGoogle Scholar
  • 20 Li JC, Xu F. Influences of light-dark shifting on the immune system, tumor growth and life span of rats, mice and fruit flies as well as on the counteraction of melatonin. Biol Signals 1997; 6: 77-89
    CrossrefPubMedGoogle Scholar
  • 21 Molinero P, Soutto M, Benot S, Hmadcha A, Guerrero JM. Melatonin is responsible for the nocturnal increase observed in serum and thymus of thymosin alpha1 and thymulin concentrations: observations in rats and humans. J Neuroimmunol 2000; 103: 180-188
    CrossrefPubMedGoogle Scholar
  • 22 Monje FJ, Cabatic M, Divisch I, Kim EJ, Herkner KR, Binder BR, Pollak DD. Constant darkness induces IL-6-dependent depression-like behavior through the NF-kapaB signaling pathway. J Neurosci 2011; 31: 9075-9083
    CrossrefPubMedGoogle Scholar
  • 23 Plytycz B, Seljelid R. Rhythms of immunity. Arch Immunol Ther Exp (Warsz) 1997; 45: 157-162
    PubMedGoogle Scholar
  • 24 Xi Y, Chen D. Partitioning the circadian clock. Science 2014; 345: 1122-1123
    CrossrefPubMedGoogle Scholar
  • 25 Kawamura M, Tasaki H, Misawa I, Chu G, Yamaguchi N, Hattori MA. Contribution of testosterone to the clock system in rat prostate mesenchyme cells. Andrology 2014; 2: 225-233
    CrossrefPubMedGoogle Scholar
  • 26 Welsh DK, Takahashi JS, Kay SA. Suprachiasmatic nucleus: cell autonomy and network properties. Annu Rev Physiol 2010; 72: 551-577
    CrossrefPubMedGoogle Scholar
  • 27 Nishide SY, Hashimoto K, Nishio T, Honma K, Honma S. Organ-specific development characterizes circadian clock gene Per2 expression in rats. Am J Physiol Regul Integr Physiol 2014; 306: R67-R74
    PubMedGoogle Scholar
  • 28 Sies H. Role of metabolic H2O2 generation: redox signaling and oxidative stress. J Biol Chem 2014; 289: 8735-8741
    CrossrefPubMedGoogle Scholar
  • 29 Stimson RH, Mohd-Shukri NA, Bolton JL, Andrew R, Reynolds RM, Walker BR. The postprandial rise in plasma cortisol in men is mediated by macronutrient-specific stimulation of adrenal and extra-adrenal cortisone production. J Clin Endocrinol Metab 2014; 99: 160-168
    CrossrefPubMedGoogle Scholar
  • 30 Vujovic N, Davidson AJ, Menaker M. Sympathetic input modulates, but does not determine, phase of peripheral circadian oscillators. Am J Phys Regul Integr Comp Physiol 2008; 295: 355-360
    PubMedGoogle Scholar
  • 31 Gary KA, Sollars PJ, Lexow N, Winokur A, Pickard GE. Thyrotropin-releasing hormone phase shifts circadian rhythms in hamsters. Neuroreport 1996; 7: 1631-1634
    CrossrefPubMedGoogle Scholar
  • 32 Pekary AE, Stevens SA, Blood JD, Sattin A. Rapid modulation of TRH and TRH-like peptide release in rat brain, pancreas, and testis by a GSK-3β inhibitor. Peptides 2010; 31: 1083-1093
    CrossrefPubMedGoogle Scholar
  • 33 Sattin A, Senanayake S, Pekary AE. Lithium modulates expression of TRH receptors and TRH-related peptides in rat brain. Neuroscience 2002; 115: 263-273
    CrossrefPubMedGoogle Scholar
  • 34 Pekary AE, Faull KF, Paulson M, Lloyd RL, Sattin A. TRH-like antidepressant peptide, pyroglutamyltyrosylprolineamide, occurs in rat brain. J Mass Spectrom 2005; 40: 1232-1236
    CrossrefPubMedGoogle Scholar
  • 35 Kubek MJ, Domb AJ, Veronesi MC. Attenuaation of kindled seizures by intranasal delivery of neuropeptide-loaded nanoparticles. Neurotherapeutics 2009; 6: 359-371
    CrossrefPubMedGoogle Scholar
  • 36 Pekary AE, Sattin A, Lloyd RL. Ketamine modulates TRH and TRH-like peptide turnover in brain and peripheral tissues of male rats. Peptides 2015; 69: 66-76
    CrossrefPubMedGoogle Scholar
  • 37 Hinkle PM, Pekary AE, Senanayaki S, Sattin A. Role of TRH receptors as possible mediators of analeptic actions of TRH-like peptides. Brain Res 2002; 935: 59-64
    CrossrefPubMedGoogle Scholar
  • 38 Pekary AE, Senanayake S, Sattin A. Cocaine regulates TRH-related peptides in rat brain. Neurochem Int 2002; 41: 415-428
    CrossrefPubMedGoogle Scholar
  • 39 Pekary AE, Sharp B, Briggs J, Carlson HE, Hershman JM. High concentrations of p-Glu-His-Pro-NH2 (Thyrotropin-Releasing Hormone) occur in rat prostate. Peptides 1983; 4: 915-919
    CrossrefPubMedGoogle Scholar
  • 40 Pekary AE, Sattin A, Meyerhoff JL, Chiligar M. Valproate modulates TRH receptor, TRH and TRH-like peptide levels in rat brain. Peptides 2004; 25: 647-658
    CrossrefPubMedGoogle Scholar
  • 41 Pekary AE, Sattin A. Rapid stimulation of TRH and TRH-like peptide release in rat brain and peripheral tissues by ghrelin and 3-Trp-ghrelin. Peptides 2012; 36: 157-167
    CrossrefPubMedGoogle Scholar
  • 42 Pekary AE, Stevens SA, Sattin A. Rapid modulation of TRH and TRH-like peptide levels in rat testis, brain and peripheral tissues by corticosterone. Neurochem Int 2006; 48: 208-217
    CrossrefPubMedGoogle Scholar
  • 43 Sattin A, Pekary AE, Blood J. Escitalopram regulates expression of TRH and TRH-like peptides in rat brain and peripheral tissues. Neuroendocrinology 2008; 88: 135-146
    CrossrefPubMedGoogle Scholar
  • 44 Fraser LR. The “switching on” of mammalian spermatozoa: molecular events involved in promotion and regulation of capacitation. Mol Reprod Dev 2010; 77: 197-208
    CrossrefPubMedGoogle Scholar
  • 45 Fraser LR. The role of small molecules in sperm capacitation. Theriogenology 2008; 70: 1356-1359
    CrossrefPubMedGoogle Scholar
  • 46 Carvalho TL, Hodson NP, Blank MA, Watson PF, Muldurry PK, Bishop AE, Gu J, Bloom SR, Polak JM. Occurrence, distribution and origin of peptide-containing nerves of guinea pig and male rat genitalia and the effects of denervation on sperm characteristics. J Anat 1986; 149: 121-141
    PubMedGoogle Scholar
  • 47 Sattin A, Pekary AE, Blood JD. Rapid modulation of TRH and TRH-like peptide release in rat brain and peripheral tissues by prazosin. Peptides 2011; 32: 1666-1676
    CrossrefPubMedGoogle Scholar
  • 48 Cano P, Jimenez-Ortega V, Larrad A, Reyes Toso CF, Cardinali DP, Esquifino AI. Effect of a high-fat diet on 24-h pattern of circulating levels of prolactin, luteinizing hormone, testosterone, corticosterone, thyroid-stimulating hormone and glucose, and pineal melatonin content, in rats. Endocrine 2008; 33: 118-125
    CrossrefPubMedGoogle Scholar
  • 49 Dauchy RT, Wren MA, Dauchy EM, Hoffman AE, Hanifin JP, Warfield B, Jablonski MR, Brainard GC, Hill SM, Mao L, Dobek GL, Dupepe LM, Blask DE. The influence of red light exposure at night on circadian metabolism and physiology in Sprague-Dawley rats. J Am Assoc Lab Anim Sci 2015; 54: 40-50
    PubMedGoogle Scholar
  • 50 Goutianos G, Tzioura A, Kyparos A, Paschalis V, Margaritelis NV, Veskoukis AS, Zafeiridis A, Dipla K, Nikolaidis MG, Vrabas IS. The rat adequately reflects human responses to exercise in blood biochemical profile: a comparative study. Physiol Rep 2015; 3: e12293
    CrossrefPubMedGoogle Scholar
  • 51 Gerendai I, Sziebert P, Gorcs T, Csaba Z, Csernus V. Effect of intratesticular administration of TRH or anti-TRH antiserum on function of rat testis. Life Sci 2000; 67: 269-281
    CrossrefPubMedGoogle Scholar
  • 52 Pekary AE, Meyer NV, Vaillant C, Hershman JM. Thyrotropin-releasing hormone and a homologous peptide in the male rat reproductive system. Biochem Biophys Res Commun 1980; 95: 993-1000
    CrossrefPubMedGoogle Scholar
  • 53 Zhao Y, Hou WG, Zhu HP, Zhao J, Wang RA, Xu RJ, Zhang YQ. Expression of thyrotropin-releasing hormone receptors in rat testis and their role in isolated Leydig cells. Cell Tissue Res 2008; 334: 283-294
    CrossrefPubMedGoogle Scholar
  • 54 Krol E, Redman P, Thomson PJ, Williams R, Mayer C, Mercer JG, Peakman JR. Effect of photoperiod on body mass, food intake and body composition in the field vole, Microtus agrestis. J Exp Biol 2005; 208 (Pt. 3) 571-584
    CrossrefPubMedGoogle Scholar
  • 55 Olayaki LA, Soladoye AO, Salman TM, Joraiah B. Effect of photoperiod on testicular function in male Sprague-Dawley rats. Niger J Physiol Sci 2008; 23: 27-30
    PubMedGoogle Scholar
  • 56 Joseph AM, Nguyen LM, Welter AE, Dominguez 2nd JM, Behnk BJ, Adhihetty PJ. Mitochondrial adaptations evoked with exercise are associated with a reduction in age-induced testicular atrophy in Fischer-344 rats. Biogerontology 2014; 15: 517-534
    CrossrefPubMedGoogle Scholar
  • 57 Wang C, Hikim AS, Ferrini M, Bonavera JJ, Vernet D, Leung A, Lue YH, Gonzalez-Cadavid NF, Swerdloff RS. Male reproductive ageing: using the brown Norway rat as a model for man. Novartis Found Symp 2002; 242: 82-95 discussion 95–97
    PubMedGoogle Scholar
  • 58 Pierpaoli W. Aging-reversing properties of thyrotropin-releasing hormone. Curr Aging Sci 2013; 6: 92-98
    CrossrefPubMedGoogle Scholar
  • 59 Apfelbach R, Blanchard CD, Blanchard RJ, Hayes RA, McGregor IS. The effects of predator odors in mammalian prey species: a review of field and laboratory studies. Neurosci Biobehav Rev 2005; 29: 1123-1144
    CrossrefPubMedGoogle Scholar
  • 60 Pekary AE, Sattin A, Blood J, Furst S. TRH and TRH-like peptide expression in rat following episodic or continuous corticosterone. Psychoneuroendocrinology 2008; 33: 1183-1197
    CrossrefPubMedGoogle Scholar
  • 61 Hu GX, Lian QQ, Lin H, Latif SA, Morris DJ, Hardy MP, Ge RS. Rapid mechanisms of glucocorticoid signaling in the Leydig cell. Steroids 2008; 73: 1018-1024
    CrossrefPubMedGoogle Scholar
  • 62 Terazono H, Mutoh T, Yamaguchi S, Kobayashi M, Akiyama M, Udo R, Ohdo S, Okamura H, Shibata S. Adrenergic regulation of clock gene expression in mouse liver. Proc Natl Acad Sci USA 2003; 100: 6795-6800
    CrossrefPubMedGoogle Scholar
  • 63 Bornstein SR, Ehrhart-Bornstein M, Scherbaum WA, Pfeiffer EF, Holst JJ. Effects of splanchnic nerve stimulation on the adrenal cortex may be mediated by chromaffin cells in a paracrine manner. Endocrinology 1990; 127: 900-906
    CrossrefPubMedGoogle Scholar
  • 64 Mitsuma T, Kayama M, Rhue N, Hirooka Y, Mori Y, Adachi K, Ping J, Nogimori T. Effect of anti-TRH-receptor antibody on corticosterone release from rat adrenal gland in vitro. Endocr Regul 1996; 30: 129-131
    PubMedGoogle Scholar
  • 65 Patton DF, Mistlberger RE. Circadian adaptations to meal timing: neuroendocrine mechanisms. Front Neurosci 2013; 7: 185
    PubMedGoogle Scholar
  • 66 Van Den Berg GJ, Beynen AC. Influence of ascorbic acid supplementation on copper metabolism in rat. Br J Nutr 1992; 68: 701-715
    CrossrefPubMedGoogle Scholar
  • 67 Tranberg B, Hansen AK, Lykkesfeldt J. High-fat feeding increases vitamin C synthesis and its circulatory mobilization in mice. Eur J Nutr 2014; 53: 1441-1444
    CrossrefPubMedGoogle Scholar
  • 68 Pekary AE, Sattin A, Blood J. Rapid modulation of TRH and TRH-like peptide release in rat brain and peripheral tissues by leptin. Brain Res 2010; 1345: 9-18
    CrossrefPubMedGoogle Scholar
  • 69 Grosbellet E, Dumont S, Schuster-Klein C, Guardiola-Lemaitre B, Pevet P, Criscuolo F, Challet E. Leptin modulates the daily rhythmicity of blood glucose. Chronobiol Int 2015; 32: 637-649
    CrossrefPubMedGoogle Scholar
  • 70 Pekary AE, Stevens SA, Sattin A. Valproate and copper accelerate TRH-like peptide synthesis in rat pancreas and reproductive tissues. Peptides 2006; 27: 2901-2911
    CrossrefPubMedGoogle Scholar
  • 71 Kulkarni RN, Wang ZL, Akinsanya KO, Bennet WM, Wang RM, Smith DM, Ghatei MA, Byfield PG, Bloom SR. Pyroglutamyl-phenylalanyl-proline amide attenuates thyrotropin-releasing hormone-stimulated insulin secretion in perifused rat islets and insulin-secreting clonal beta-cell lines. Endocrinology 1995; 136: 5155-5164
    CrossrefPubMedGoogle Scholar
  • 72 Benicky J, Strbak V. Glucose stimulates and insulin inhibits release of pancreatic TRH in vitro. Eur J Endocrinol 2000; 142: 60-65
    CrossrefPubMedGoogle Scholar
  • 73 Pekary AE, Sattin A. Increased TRH and TRH-like peptide release in rat brain and peripheral tissues during proestrus/estrus. Peptides 2014; 52: 1-10
    CrossrefPubMedGoogle Scholar
  • 74 Suzuki M, Honda Y, Li MZ, Masuko S, Murata Y. The localization of oxytocin receptors in the islets of Langerhans in the rat pancreas. Regul Pept 2013; 183: 42-45
    CrossrefPubMedGoogle Scholar
  • 75 Pekary AE, Sattin A. Carbetocin stimulates release of TRH and TRH-like peptides throughout the male rat brain and peripheral tissues. Society for Neuroscience, Annual Meeting, Submitted
    PubMedGoogle Scholar
  • 76 Bhasin S, Pekary AE, Brunskill B, Hershman JM, Swerdloff RS. Hormonal control of prostatic thyrotropin-releasing hormone (TRH): testosterone modulates prostatic TRH concentration. Endocrinology 1984; 114: 946-950
    CrossrefPubMedGoogle Scholar
  • 77 Pekary AE, Lukaski HC, Mena I, Smith SM, Bhasin S, Hershman JM. Testosterone increases TRH biosynthesis in epididymis but not heart of zinc-deficient rats. Peptides 1993; 14: 315-324
    CrossrefPubMedGoogle Scholar