The cellular and molecular mechanisms through which the melatonin signal is decoded to drive/synchronize photoperiodic responses remain unclear. Much of our current understanding of the processes involved in this readout derives from studies of melatonin action in the pars tuberalis of the anterior pituitary. Here, the authors review current knowledge and highlight critical gaps in our present understanding.
Barrett P , Choi WS, Morris M, and Morgan P (2000) Arole for tyrosine phosphorylation in the regulation and sensitization of adenylate cyclase by melatonin. FASEB J14:1619-1628.
2.
Barrett P , MacLean A, Davidson G, and Morgan PJ (1996) Regulation of the Mel 1a melatonin receptor mRNA and protein levels in the ovine pars tuberalis: Evidence for a cyclic adenosine 3[.minute],5[.minute]-monophosphate-independent Mel 1a receptor coupling and an autoregulatory mechanism expression. Mol Endocrinol10:892-902.
3.
Bartness TJ and Goldman BD (1989) Mammalian pineal melatonin—A clock for all seasons. Experientia45:939-945.
4.
Bartness TJ , Powers JB, Hastings MH, Bittman EL, and Goldman BD (1993) The timed infusion paradigm for melatonin delivery—What has it taught us about the melatonin signal, its reception, and the photoperiodic control of seasonal responses?J Pineal Res15:161-190.
5.
Browning C , Beresford I, Fraser N, and Giles H (2000) Pharmacological characterization of human recombinant melatonin mt(1) and Mt2 receptors. Br J Pharmacol129:877-886.
6.
Brydon L , Roka F, Petit L, De Coppet P, Tissot M, Barrett P, Morgan PJ, Nanoff C, Strosberg AD, and Jockers R (1999) Dual signaling of human Mel1a melatonin receptors via G(i2), G(i3), and G(q/11) proteins. Mol Endocrinol13:2025-2038.
7.
Carlson LL , Weaver DR, and Reppert SM (1991) Melatonin receptors and signal transduction during development in Siberian hamsters (Phodopus-sungorus). Dev Brain Res59:83-88.
8.
Delaescalera GM , Guthrie J, and Weiner RI (1988) Transient removal of dopamine potentiates the stimulation of prolactin-release by TRH but not VIP—stimulation via Ca 2+/protein kinase-C pathway. Neuroendocrinology47:38-45.
9.
Delaescalera GM and Weiner RI (1988) Mechanism(s) by which the transient removal of dopamine regulation potentiates the prolactin-releasing action of thyrotropinreleasing-hormone. Neuroendocrinology47:186-193.
10.
Ebisawa T , Karne S, Lerner MR, and Reppert SM (1994) Expression cloning of a high-affinity melatonin receptor from Xenopus dermal melanophores. Proc Natl Acad Sci U S A91:6133-6137.
11.
Fleming JV , Barrett P, Coon SL, Klein DC, and Morgan PJ (1999) Ovine arylalkylamine N-acetyltransferase in the pineal and pituitary glands: Differences in function and regulation. Endocrinology14:972-978.
12.
Godson C and Reppert SM (1997) The Mel(1a) melatonin receptor is coupled to parallel signal transduction pathways. Endocrinology138:397-404.
13.
Goldman BD (2001) Mammalian photoperiodic system: Formal properties and neuroendocrine mechanisms of photoperiodic time measurement. J Biol Rhythms16:283-301.
14.
Graham ES , Hazlerigg DG, and Morgan PJ (1999) Evidence for regulation of basic fibroblast growth factor gene expression by photoperiod and melatonin in the ovine pars tuberalis. Mol Cell Endocrinol156:45-53.
15.
Grosse J , Maywood ES, Ebling FJP, and Hastings MH (1993) Testicular regression in pinealectomized Syrian-hamsters following infusions of melatonin delivered on noncircadian schedules. Biol Reprod49:666-674.
16.
Hazlerigg DG , Gonzalez-Brito A, Lawson W, Hastings MH, and Morgan PJ (1993) Prolonged exposure to melatonin leads to time-dependent sensitization of adenylate-cyclase and down-regulates melatonin receptors in pars tuberalis cells from ovine pituitary. Endocrinology132:285-292.
17.
Hazlerigg DG , Hastings MH, and Morgan PJ (1994) The recovery of ovine pars tuberalis cells from melatonin-induced sensitization is a slow, protein synthesis-dependent phenomenon. J Endocrinol142: 127-138.
18.
Hazlerigg DG , Hastings MH, and Morgan PJ (1996a) Production of a prolactin releasing factor by the ovine pars tuberalis. J Neuroendocrinol8:489-492.
19.
Hazlerigg DG , Morgan PJ, Lawson W, and Hastings MH (1991) Melatonin inhibits the activation of cyclic AMP-dependent protein-kinase in cultured pars tuberalis cells from ovine pituitary. J Neuroendocrinol3:597-603.
20.
Hazlerigg DG , Thompson M, Hastings MH, and Morgan PJ (1996b) Regulation of mitogen-activated protein kinase in the pars tuberalis of the ovine pituitary: Interactions between melatonin, insulin-like growth factor-1, and forskolin. Endocrinology137:210-218.
21.
Lincoln GA and Clarke IJ (1994) Photoperiodically-induced cycles in the secretion of prolactin in hypothalamopituitary disconnected rams—Evidence for translation of the melatonin signal in the pituitary-gland. J Neuroendocrinol6:251-260.
22.
Lincoln GA and Maeda KI (1992) Effects of placing micro-implants of melatonin in the mediobasal hypothalamus and preoptic area on the secretion of prolactin and beta-endorphin in rams. J Endocrinol134:437-448.
23.
Liu C , Weaver DR, Jin XW, Shearman LP, Pieschl RL, Gribkoff VK, and Reppert SM (1997) Molecular dissection of two distinct actions of melatonin on the suprachiasmatic circadian clock. Neuron19:91-102.
24.
Malpaux B , Daveau A, Maurice-Mandon F, Duarte G, and Chemineau P (1998) Evidence that melatonin acts in the premammillary hypothalamic area to control reproduction in the ewe: Presence of binding sites and stimulation of luteinizing hormone secretion by in situ microimplant delivery. Endocrinology139:1508-1516.
25.
Malpaux B , Migaud M, Tricoire H, and Chemineau P (2001) Biology of mammalian photoperiodism and the critical role of the pineal gland and melatonin. J Biol Rhythms16:336-347.
26.
Maywood ES and Hastings MH (1995) Lesions of the iodomelatonin-binding sites of the mediobasal hypothalamus spare the lactotropic, but block the gonadotropic response of male Syrian-hamsters to short photoperiod and to melatonin. Endocrinology136:144-153.
27.
Mcnulty S , Ross AW, Barrett P, Hastings MH, and Morgan PJ (1994) Melatonin regulates the phosphorylation of CREB in ovine pars tuberalis. J Neuroendocrinol6:523-532.
28.
McNulty S , Ross AW, Shiu KY, Morgan PJ, and Hastings MH (1996) Phosphorylation of CREB in ovine pars tuberalis is regulated both by cyclic AMP-dependent and cyclic AMP-independent mechanisms. J Neuroendocrinol8:635-645.
29.
Messager S , Garabette ML, Hastings MH, and Hazlerigg DG (2001) Tissue-specific abolition of Per1 expression in the pars tuberalis by pinealectomy in the Syrian hamster. Neuroreport12:579-582.
30.
Messager S , Hazlerigg DG, Mercer JG, and Morgan PJ (2000) Photoperiod differentially regulates the expression of Per1 and ICER in the pars tuberalis and the suprachiasmatic nucleus of the Siberian hamster. Eur J Neurosci12:2865-2870.
31.
Messager S , Ross AW, Barrett P, and Morgan PJ (1999) Decoding photoperiodic time through Per1 and ICERgene amplitude. Proc Natl Acad Sci USA96:9938-9943.
32.
Morgan PJ (1994) Molecular signalling via the melatonin receptor. Adv Pineal Res5:191-197.
33.
Morgan PJ (2000) The pars tuberalis: The missing link in the photoperiodic regulation of prolactin secretion?J Neuroendocrinol12:287-295.
34.
Morgan PJ , Barrett P, Howell HE, and Helliwell R (1994) Melatonin receptors—Localization, molecular pharmacology and physiological significance. Neurochem Int24:101-146.
35.
Morgan PJ , Davidson G, Lawson W, and Barrett P (1990) Both pertussis toxin-sensitive and insensitive G-proteins link melatonin receptor to inhibition of adenylate-cyclase in the ovine pars tuberalis. J Neuroendocrinol2:773-776.
36.
Morgan PJ , Lawson W, and Davidson G (1991) Interaction of forskolin and melatonin on cyclic-AMP generation in pars tuberalis cells of ovine pituitary. J Neuroendocrinol3:497-501.
37.
Morgan PJ , Williams LM, Davidson G, Lawson W, and Howell HE (1989) Melatonin receptors on ovine pars tuberalis—Characterization and autoradiographical localization. J Neuroendocrinol1:1-4.
38.
Morgan PJ , Webster CA, Mercer JG, Ross AW, Hazlerigg DG, Maclean A, and Barrett P (1996) The ovine pars tuberalis secretes a factor(s) that regulates gene expression in both lactotropic and nonlactotropic pituitary cells. Endocrinology137:4018-4026.
39.
Nuesslein-Hildesheim B , O'brien JA, Ebling JP, Maywood ES, and Hastings MH (2000) The circadian cycle of mPerclock gene products in the suprachiasmatic nucleus of the Siberian hamster encodes both daily and seasonal time. Eur J Neurosci12:2856-2864.
40.
Oishi K , Murai I, Sakamoto K, Otsuka H, Miyake Y, Nagase T, and Ishida N (2000) The pineal gland is not essential for circadian expression of rat period homologue (rPer2) mrna in the suprachiasmatic nucleus and peripheral tissues. Brain Res885:298-302.
41.
Pelisek V and Vanecek J (2000) Different effects of melatonin pretreatment on cAMP and LH responses of the neonatal rat pituitary cells. J Pineal Res28:234-241.
42.
Pitrosky B , Kirsch R, Vivienroels B, Georgbentz I, Canguilhem B, and Pevet P (1995) The photoperiodic response in Syrian-hamster depends upon a melatonin-driven circadian-rhythm of sensitivity to melatonin. J Neuroendocrinol7:889-895.
43.
Reppert SM , Godson C, Mahle CD, Weaver DR, Slaugenhaupt SA, and Gusella JF (1995) Molecular characterization of a 2nd melatonin receptor expressed in human retina and brain—The mel(1b) melatonin receptor. Proc Natl Acad Sci U S A92:8734-8738.
44.
Reppert SM , Weaver DR, and Ebisawa T (1994) Cloning and characterization of a mammalian melatonin receptor that mediates reproductive and circadian responses. Neuron13:1177-1185.
45.
Ross AW , Barrett P, Mercer JG, and Morgan PJ (1996) Melatonin suppresses the induction of AP-1 transcription factor components in the pars tuberalis of the pituitary. Mol Cell Endocrinol123:71-80.
46.
Sakamoto K , Nagase T, Fukui H, Horikawa K, Okada T, Tanaka H, Sato K, Miyake Y, Ohara O, Kako K, and Ishida N (1998) Multitissue circadian expression of rat period homolog (rPer2) mRNA is governed by the mammalian circadian clock, the suprachiasmatic nucleus in the brain. J Biol Chem273:27039-27042.
47.
Stehle JH , Foulkes NS, Molina CA, Simonneaux V, Pevet P, and Sassonecorsi P (1993) Adrenergic signals direct rhythmic expression of transcriptional repressor CREM in the pineal-gland. Nature365:314-320.
48.
Sun ZS , Albrecht U, Zhuchenko O, Bailey J, Eichele G, and Lee CC (1997) RIGUI, a putative mammalian ortholog of the Drosophila period gene. Cell90:1003-1011.
49.
Tamarkin L , Westrom WK, and Hammill AI (1976) Effect of melatonin on the reproductive systems of male and female Syrian hamsters: A diurnal rhythm of sensitivity to melatonin. Endocrinology99:1534-1541.
50.
Valenti S , Guido R, Giusti M, and Giordano G (1995) In-vitro acute and prolonged effects of melatonin on purified rat leydig-cell steroidogenesis and adenosine-3[.minute],5[.minute]-monophosphate production. Endocrinology136:5357-5362.
51.
Vanecek J and Klein DC (1992) Sodium-dependent effects of melatonin on membrane-potential of neonatal rat pituitary-cells. Endocrinology131:939-946.
52.
Vanecek J and Vollrath L (1990) Melatonin modulates diacylglycerol and arachidonic-acid metabolism in the anterior-pituitary of immature rats. Neurosci Lett110:199-203.
53.
Weaver DR , Liu C, and Reppert SM (1996) Nature's knockout: The Mel(1b) receptor is not necessary for reproductive and circadian responses to melatonin in Siberian hamsters. Mol Endocrinol10:1478-1487.
54.
Witt-Enderby PA , Masana MI, and Dubocovich ML (1998) Physiological exposure to melatonin supersensitizes the cyclic adenosine 3[.minute],5[.minute]-monophosphate-dependent signal transduction cascade in Chinese hamster ovary cells expressing the human mt(1) melatonin receptor. Endocrinology139:3064-3071.
