CLOCK IN PITUITARY · Role of the circadian clockwork in the anterior pituitary gland
FP6 — Marie Curie Actions (Human Resources and Mobility)
- Duration
- 2004-06-30 → 2005-06-29
- EU contribution
- €40,000
- Participants
- 1
- Scheme
- ERG
Lines connect the coordinator with its partners.
Results in brief
Final Activity Report Summary - CLOCK IN PITUITARY (Role of the circadian clockwork in the anterior pituitary gland)
The pituitary gland is the master gland of the endocrine system that regulates a number of physiological functions such as growth or reproduction. The release of its hormones in the bloodstream is under the control of hypothalamic oscillators that pace the pulsatile pattern of each pituitary hormone. In this project, we proposed to investigate the circadian clock gene in the pituitary gland. We described their temporal pattern of expression, which permitted us to define this gland as a peripheral clock. However, we found that the regulation of clock genes is much more complex in the pituitary than in other peripheral organs, revealing an integration of different cues, such as light influence through the suprachiasmatic nuclei and feeding schedule. The use of mutant mice that lack a functional circadian clock disclosed a dramatic dampening in pituitary pulsatility, namely of the highly patterned secretion of growth hormone (GH) in males. Interestingly, this change of GH pattern has unexpected consequences at the metabolic level since expression of hepatic enzymes involved in xenobiotic detoxification is altered.
Data: CORDIS, © European Union
Project objective
The aim of this proposal is to investigate the physiological relevance of the molecular circadian clockwork expressed in peripheral organs. This question will be addressed in a new and original paradigm: the endocrine pituitary gland. Indeed, several so-called clock genes that form the molecular cogwheels of the biological clock have recently been identified. Surprisingly, besides being activated in structures known to host an internal clock (namely the suprachiasmatic nuclei, SCN, in mammals) they are also expressed in many -if not all- other tissues, among which the pituitary gland where strong oscillations of the clock machinery have been found. Using mutant mice that bear an altered clock, we will research the impact of the clock upon several key parameters of the gland physiology such as electrical activity of endocrine cells and hormonal secretion in basal and stimulated conditions.This project constitutes the frame of a stable research position of the applicant in his native country. It will be achieved thanks to several scientific collaborations at the national, European and worldwide levels. Results obtained from this research are expected to answer critical questions in fundamental chronobiology and cell biology but also, the understanding of the fine mechanisms that pace the daily functioning of organs may have potential important outcomes in modern medicine, e.g. development of chronotherapy.
Original text from CORDIS.
Participants
- INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE · PARISCoordinatorFrance
Links
Data: CORDIS, © European Union