Cervical stimulation activates A1 and locus coeruleus neurons that project to the paraventricular nucleus of the hypothalamus.

In female rats, stimulation of the uterine cervix during mating induces two daily surges of prolactin. Inhibition of hypothalamic dopamine release and stimulation of oxytocin neurons in the paraventricular nucleus (PVN) are required for prolactin secretion. We aim to better understand how stimulation of the uterine cervix is translated into two daily prolactin surges.

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.

The rhythmic secretion of mating-induced prolactin secretion is controlled by prolactin acting centrally.

Artificial copulomimetic cervical stimulation (CS) induces an immediate release of oxytocin (OT) and prolactin (PRL) followed by a daily PRL rhythm characterized by nocturnal and diurnal surges. Although we have shown that the initial release of PRL is induced by the immediate release of OT, we tested whether the PRL that is released in response to CS is responsible for the initiation and maintenance of the subsequent PRL surges. Thus, we injected OVX rats centrally or peripherally with ovine PRL (oPRL) at 2200 h.

Knockdown of clock genes in the suprachiasmatic nucleus blocks prolactin surges and alters FRA expression in the locus coeruleus of female rats.

The nature of the circadian signal from the suprachiasmatic nucleus (SCN) required for prolactin (PRL) surges is unknown. Because the SCN neuronal circadian rhythm is determined by a feedback loop of Period (Per) 1, Per2, and circadian locomotor output cycles kaput (Clock) gene expressions, we investigated the effect of SCN rhythmicity on PRL surges by disrupting this loop. Because lesion of the locus coeruleus (LC) abolishes PRL surges and these neurons receive SCN projections, we investigated the role of SCN rhythmicity in the LC neuronal circadian rhythm as a possible component of the circadian mechanism regulating PRL surges.

Oxytocin action at the lactotroph is required for prolactin surges in cervically stimulated ovariectomized rats.

Cervical stimulation induces two daily rhythmic prolactin surges, nocturnal and diurnal, which persist for several days. We have shown that a bolus injection of oxytocin initiates a similar prolactin rhythm, which persists despite low levels of oxytocin after injection. This suggests that oxytocin may trigger the cervical stimulation-induced rhythmic prolactin surges.

Anatomical and functional characterization of clock gene expression in neuroendocrine dopaminergic neurons.

Oscillations of gene expression and physiological activity in suprachiasmatic nucleus (SCN) neurons result from autoregulatory feedback loops of circadian clock gene transcription factors. In the present experiment, we have determined the pattern of PERIOD1 (PER1), PERIOD2 (PER2), and CLOCK expression within neuroendocrine dopaminergic (DAergic) neurons (NDNs) of ovariectomized (OVX) rats. We have also determined the effects of per1, per2, and clock mRNA knockdown in the SCN with antisense deoxyoligonucleotides (AS-ODN) on DA release from NDNs.