Central Clock Regulates the Cervically Stimulated Prolactin Surges by Modulation of Dopamine and Vasoactive Intestinal Polypeptide Release in Ovariectomized Rats

Background/Aims: Cervical stimulation induces a circadian rhythm of prolactin secretion and antiphase dopamine release. The suprachiasmatic nucleus (SCN) controls this rhythm, and we propose that it does so through clock gene expression within the SCN. Methods: To test this hypothesis, serial blood samples were taken from animals injected with an antisense deoxyoligonucleotide cocktail for clock genes (generated against the 5' transcription start site and 3' cap site of per1, per2, and clock mRNA) or with a random-sequence deoxyoligonucleotide in the SCN. To determine whether disruption of clock genes in the SCN compromises the neural mechanism controlling prolactin secretion, we sacrificed another group of rats (under the same treatments) at 12.00 or 17.00 h. Dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) were measured using HPLC/electrochemical detection in the median eminence as well as the intermediate and the neural lobe of the pituitary gland, and the DOPAC: dopamine ratio was used as an index of dopamine activity. Vasoactive intestinal polypeptide (VIP) content was determined in tissue punches of the SCN and paraventricular nucleus (PVN), an SCN efferent. Results: Treatment with clock gene antisense deoxyoligonucleotide cocktail abolished both the diurnal and nocturnal prolactin surges induced by cervical stimulation. This treatment abolished the antiphase relationship established by cervical stimulation between dopamine neuronal activity and prolactin secretion. Also, VIP content increased in the SCN and decreased in the PVN. Conclusion: These results suggest that the SCN clock determines the circadian rhythm of prolactin secretion in cervically stimulated rats by regulating dopamine neuronal activity and VIP inputs to the PVN. Copyright (C) 2009 S. Karger AG, Basel