Elsevier

Brain Research

Volume 901, Issues 1–2, 18 May 2001, Pages 109-116
Brain Research

Research report
The stimulatory effect of vasopressin on the luteinizing hormone surge in ovariectomized, estradiol-treated rats is time-dependent

https://doi.org/10.1016/S0006-8993(01)02309-5Get rights and content

Abstract

The luteinizing hormone surge in the female rat is not only induced by the positive feedback of estradiol, but also by circadian signals originating in the suprachiasmatic nucleus (SCN). In a previous study we showed that administration of vasopressin, an SCN transmitter present in preoptic projections, induced an LH surge in animals bearing complete lesions of the SCN. This strongly suggests vasopressin as a stimulatory circadian signal for the timing of the LH surge. In the present study we investigated during which time window vasopressin may act in the medial preoptic area to stimulate LH secretion in SCN-intact female rats. Vasopressin or a specific V1a receptor antagonist was administered into the MPO by a reverse microdialysis technique during different time windows, and plasma LH concentrations were measured. Vasopressin stimulated the LH surge in 30% of the animals, when administered during the second half of the light period, but during the first half of the light period no effects were observed. Administration of the V1a receptor antagonist, however, did not affect the LH surge. These data confirm our previous results that vasopressin is a stimulatory factor for the LH surge also in SCN-intact animals, and indicate that a certain time window is available for such stimulation. We hypothesize that vasopressin in the SCN-intact animal may act as a circadian signal during a specific time window to induce the LH surge. The time window is the result of other SCN regulatory systems that are involved in the preparation of the LH surge.

Introduction

The preovulatory luteinizing hormone (LH) surge of the female rat requires two types of signals, i.e. an ovarian signal and a circadian signal. The ovarian signal consists of rising levels of estradiol (E2) secreted by the developing follicles. E2 provides a positive feedback signal via estrogen-receptor (ER)-containing neurons in the medial preoptic area (MPO), resulting in activation of the gonadotropin-releasing hormone (GnRH) neurons and thereby in the LH surge [17], [30]. The circadian signal arises in the suprachiasmatic nucleus (SCN) of the hypothalamus, which projects to the ER neurons in the MPO and provides a time window during which the surge can be induced [3], [4], [13], [37]. The crucial importance of the MPO, SCN and E2 has been demonstrated by lesion studies [6], [38].

In a previous study, the nature of the stimulatory circadian signal was investigated [29]. Based on the fact that the SCN is a major source of vasopressin (VP) fibers in the MPO [14], [36], [37] and the importance of rhythmically released VP as a circadian signal for the corticosterone rhythm [19], [21], we hypothesized that rhythmical release of VP by SCN terminals in the MPO may comprise a circadian signal for the LH surge. We demonstrated that in SCN-lesioned animals, which do not show spontaneous LH surges [25], VP administration in the MPO induced a full LH surge independent on the time of administration [29]. These results suggested that VP in the MPO acted as a trigger for the initiation of the LH surge, likely mimicking the original circadian signal from the SCN.

In the present study, we aimed to investigate whether VP administration in SCN-intact animals could reveal the time window for VP-induced activation of the LH surge. A sensitive time window several hours prior to LH surge has been long described, and it is thought that the circadian signal occurs in this time window [6]. The endogenous secretion of VP by SCN neurons increases during the first half of the light period, and peaks in the middle of the day, during the sensitive time window prior to the LH surge. After the peak, VP secretion declines, reaching a trough in the dark period [15], [20]. To investigate when VP may activate the GnRH system, VP or a specific V1a receptor (V1aR) antagonist was administered at different moments relative to the endogenous VP rhythm. Unilateral administration of VP was performed during the increasing or decreasing phase of the VP rhythm to investigate if VP at these moments may advance or enhance the LH surge. To investigate the endogenous role of VP, preoptic V1a receptors [28] were blocked when VP secretion was maximal, and when VP secretion gradually increased. These experiments were performed in ovariectomized, E2-treated rats, which show daily LH surges. Performing VP administration and blood sampling simultaneously enabled us to investigate both acute and delayed effects on the afternoon LH surges.

Section snippets

Animals

Adult female Wistar rats bred at our lab facilities from HcdCpd:WU animals (Harlan, Zeist, the Netherlands) were housed in a temperature controlled room at a regular 12:12 light–dark (LD) schedule with food and water available ad libitum. The time of day for the LD schedule was varied between animal groups, depending on the time window of VP or V1aR antagonist administration. Therefore all data are shown relative to the moment of lights on, which is expressed as Zeitgeber time (ZT) 0, and

Results

In the present experimental conditions, the proestrus LH surge had an average peak and peaktime of 44.5±8.2 ng/ml and 11.3±0.3 h, respectively. E2-induced LH surges in control animals have a significantly lower amplitude (4–6.3 ng/ml) compared to the proestrus surge (P<0.005), and this amplitude was unaffected by the different moments of microdialysis. The peaktime was comparable between proestrus and Ringer-treated OVX+E2 animals, with the exception of ZT 4–7 Ringer-dialyzed animals, which

Discussion

In the present study, VP administration in the MPO of SCN-intact, OVX, E2-treated rats stimulated the amplitude of the LH surge, without altering the peaktime. This effect occurred in eight of 26 animals dialyzed with VP from ZT 7.5–12.5 (VP-H), while in the other 18 animals (VP-L) and in animals dialyzed from ZT 0–5, VP did not affect the LH surge. VP-H and VP-L animals could not be distinguished on age, probe localizations or plasma E2, prolactin or corticosterone concentrations (unpublished

Acknowledgements

We would like to thank Joke Wortel and Jan van der Vliet for assistance with surgery, Hans Swarts for assistance with radioimmunoassays. This work was financially supported by NWO-grant 903-43-120.

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