Inge F Palm

Melatonin sees the light: blocking GABA-ergic transmission in the paraventricular nucleus induces daytime secretion of melatonin.

Despite a pronounced inhibitory effect of light on pineal melatonin synthesis, usually the daily melatonin rhythm is not a passive response to the surrounding world. In mammals, and almost every other vertebrate species studied so far, the melatonin rhythm is coupled to an endogenous pacemaker, i.e. a circadian clock. In mammals the principal circadian pacemaker is located in the suprachiasmatic nuclei (SCN), a bilateral cluster of neurons in the anterior hypothalamus. In the present paper we show in the rat that bilateral abolition of γ‐aminobutyric acid (GABA), but not vasopressin, neurotransmission in an SCN target area, i.e. the paraventricular nucleus of the hypothalamus, during (subjective) daytime results in increased pineal melatonin levels. The fact that complete removal of the SCN results in a pronounced increase of daytime pineal mRNA levels for arylalkylamine N‐acetyltransferase (AA‐NAT), i.e. the rate‐limiting enzyme of melatonin synthesis, further substantiates the existence of a major inhibitory SCN output controlling the circadian melatonin rhythm.

VASOPRESSIN INDUCES A LUTEINIZING HORMONE SURGE IN OVARIECTOMIZED, ESTRADIOL-TREATED RATS WITH LESIONS OF THE SUPRACHIASMATIC NUCLEUS

The luteinizing hormone surge in the female rat is the result of the integration of multiple signals within the medial preoptic area. The medial preoptic area contains gonadotropin-releasing hormone neurons that are responsible for the release of luteinizing hormone, neurons containing estrogen receptors and terminals originating from the suprachiasmatic nucleus with, for example, vasopressin as neurotransmitter. Both the medial preoptic area and suprachiasmatic nucleus are crucial for the occurrence of luteinizing hormone surges, since lesioning of either nucleus prevents pre-ovulatory and steroid-induced luteinizing hormone surges. In this study, we investigated whether vasopressin in the medial preoptic area could be the daily neuronal signal from the suprachiasmatic nucleus responsible for the timing of the luteinizing hormone surge. Vasopressin (50 ng/microl) or Ringer solution was administered by reverse microdialysis from Zeitgeber times 7.5 to 12.5 into the medial preoptic area of ovariectomized, estradiol-treated rats. The suprachiasmatic nucleus was lesioned to remove all cyclic luteinizing hormone secretion. This was evaluated by monitoring behavioral activity; animals that were arrhythmic were included in the experiments. Hourly blood samples were taken to measure plasma luteinizing hormone levels. Preoptic vasopressin administration induced a surge-like luteinizing hormone pattern in suprachiasmatic nucleus-lesioned animals, whereas constant, basal luteinizing hormone levels were found in the control animals. These data show that vasopressin, by itself, is able to trigger the luteinizing hormone surge in suprachiasmatic nucleus-lesioned rats. We propose that vasopressin is a timing signal from the suprachiasmatic nucleus responsible for the activation of the hypothalamo-pituitary-gonadal axis in the female rat.

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

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.

Control of the Estradiol-Induced Prolactin Surge by the Suprachiasmatic Nucleus

In the present study we investigated how the suprachiasmatic nucleus (SCN) controls the E(2)-induced PRL surge in female rats. First, the role of vasopressin (VP), a SCN transmitter present in medial preoptic area (MPO) projections and rhythmically released by SCN neurons, as a circadian signal for the E(2)-induced PRL surge was investigated. Using a reverse microdialysis technique, VP was administered in the MPO during the PRL surge, resulting in a suppression of the surge. VP administration before the surge did not affect PRL secretion. Also, administration of a V1a receptor antagonist before the surge was ineffective. Second, lesions of the SCN were made that resulted in constant basal PRL levels, suggesting that with removal of the SCN a stimulatory factor for PRL secretion disappeared. Indeed, the PRL secretory response to blockade of pituitary dopamine receptors was significantly reduced in SCN-lesioned animals. These data suggest that the afternoon decrease of VP release in the MPO by SCN terminals enables the PRL surge to occur, and may thus be a circadian signal for the PRL surge. Simultaneously the SCN is involved in the regulation of the secretory capacity of the pituitary, possibly via specific PRL-releasing factors.

Central vasopressin systems and steroid hormones.

Publisher Summary This chapter discusses central vasopressin (VP) systems and steroid hormones. VP is released from neurons residing in the supraoptic (SON) and paraventricular nucleus (PVN) that projects to the posterior pituitary. Using a wide variety of different techniques, the largest part of the VPergic innervation in the brain is traced back to four major VP systems: (1) the sexually dimorphic system, with VP neurons localized in the bed nucleus of the stria terminalis (BNST) and the medial amygdala (AME), (2) the autonomic, (3) endocrine system originating from parvocellular VP neurons located in the PVN, and (4) the biological clock system derived from VP neurons located in the suprachiasmatic nucleus (SCN). Steroid hormones and central VP systems interact in a variety of ways. The clearest example is presented by the sexually dimorphic system that shows a complete disappearance in the absence of gonadal steroids. The chapter describes the effect of VP on steroid hormones. A large number of experiments have indicated an effect of gonadal steroids on the VP system that projects to the bloodstream. The effects on the magnocellular VP system that result from the direct influence of steroid hormones on magnocellular VP neurons or involve indirect effects of steroid hormones affecting the central regulation of VP secretion from the posterior pituitary are discussed.

Body Weight Cycling with Identical Diet Composition Does Not Affect Energy Balance and Has No Adverse Effect on Metabolic Health Parameters

Background: Body weight (BW) cycling, the yo-yo effect, is generally thought to have adverse effects on human metabolic health. However, human and animal experiments are limited in number and do not provide clear answers, partly due to large variations in experimental design, parameters measured, and definitions of BW cycling. Here, we examined the effect of repetitive BW cycling versus single- and non-cycling control groups, without alterations in diet composition, on steady state BW and metabolic parameters. Methods: We induced well-defined BW cycles on a semi-purified high fat diet in C57BL/6J mice, a well-described animal model for diet-induced obesity, and measured energy expenditure and relevant metabolic parameters. Results: Our setup indeed resulted in the intended BW changes and always reached a stage of energy balance. A history of weight cycling did not result in increased BW or fat mass compared with the control group, nor in deteriorated serum concentrations of glucose, adipokines and serum triglyceride and free fatty acid (FFA) concentrations. If anything, BW tended to be reduced, presumably because of a reduced overall energy intake in BW cycling animals. Conclusion: Repeated cycling in BW without changes in diet composition does not lead to impaired metabolic health nor increased BW (gain).