Targeted deletions of Mel1a and Mel1b melatonin receptors affect pCREB levels in lactotroph and pars intermedia cells of mice.
The actions of the pineal hormone melatonin depend on two types of membrane-bound, G-protein-coupled receptors: the MT1 (Mel1a) and MT2 (Mel1b) melatonin receptors. An important target of melatonin is the hypophysial pars tuberalis that controls the activity of lactotroph cells in the pars distalis (PD). To identify the melatonin receptor type responsible for regulation of the lactotroph cells in pars distalis we studied the levels of Ser133-phosphorylated pCREB in immunocytochemically identified lactotroph cells of wild-type mice (MelAABB) and of mice bearing targeted deletions of the Mel1a receptor (MelaaBB), the Mel1b receptor (MelAAbb) or of both receptor types (Melaabb) at five different time points of a light/dark cycle. Moreover, we analyzed whether pCREB levels in pars intermedia cells also depend on intact melatonin signal transduction cascades. In wild type and MelAAbb mice the percentage of lactotroph cells with nuclear pCREB immunoreactions varied significantly over a 24 h period, whereas in MelaaBB and Melaabb mice no significant differences were found between the five time points analyzed. pCREB levels in the pars intermedia did not show rhythmic variation in wild type or Melaabb animals but wild type mice had higher pCREB levels than Melaabb. Our results indicate that Mel1a and Mel1b melatonin receptors are involved in the control of the activity state of lactotroph and pars intermedia cells of mice.
Sheynzon
Pjotr
P
Dr. Senckenbergische Anatomie, Institut für Anatomie II, Fachbereich Medizin der J.W. Goethe-Universität Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt/Main, Germany.
Korf
Horst-Werner
HW
D000704:Analysis of Variance; D000818:Animals; D050882:CREB-Binding Protein / Q000378:metabolism*; D002452:Cell Count / Q000379:methods; D018797:Cell Cycle Proteins; D002467:Cell Nucleus / Q000378:metabolism; D002940:Circadian Rhythm / Q000502:physiology; D003593:Cytoplasm / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000378:metabolism; D056950:Period Circadian Proteins; D010902:Pituitary Gland / Q000166:cytology* / Q000378:metabolism*; D011388:Prolactin / Q000378:metabolism; D044122:Receptor, Melatonin, MT1 / Q000172:deficiency / Q000502:physiology*; D044123:Receptor, Melatonin, MT2 / Q000172:deficiency / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; C539023:Per1 protein, mouse; D056950:Period Circadian Proteins; D044122:Receptor, Melatonin, MT1; D044123:Receptor, Melatonin, MT2; D011388:Prolactin; D050882:CREB-Binding Protein