The hypophysial pars tuberalis transduces photoperiodic signals via multiple pathways and messenger molecules

Located between the median eminence, the portal vessels, and the pars distalis (PD) of the hypophysis, the hypophysial pars tuberalis (PT) is an important center for transmission of photoperiodic information to neuroendocrine circuits involved in the control of reproduction, metabolism and behavior. Despite enormous and long lasting efforts, output pathways and messenger molecules from the PT have been unraveled only recently. Most interestingly, the PT sends its signals in two directions: via a "retrograde" pathway to the hypothalamus and via an "anterograde" pathway to the PD. TSH has been identified as a messenger of the "retrograde" pathway. As discovered in Japanese quail, TSH triggers molecular cascades mediating thyroid hormone conversion in the mediobasal hypothalamus (MBH) to activate the gonadal axis. These molecular mechanisms are conserved in photoperiodic mammals, and even in non-photoperiodic laboratory mice. The search for molecules of the "anterograde" pathway was for a long time focused on PT-specific neuropeptides, the so-called "tuberalins". The discovery of a PT-intrinsic endocannabinoid system in hamsters which is regulated by the photoperiod provides strong experimental evidence that the PT also synthesizes lipidergic messengers. To date, 2-arachidonoylglycerol (2-AG) appears as the most important lipidergic messenger from the PT. The primary target of 2-AG, the cannabinoid receptor 1 (CB1) is expressed in the hamster PD. A PT-intrinsic endocannabinoid system also exists in man and CB1 receptors are demonstrated in ACTH-producing cells and folliculo-stellate cells of the human PD. These data lend support to the hypothesis that endocannabinoids function as messengers of the anterograde pathway.