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BACKGROUND/AIMS: A mammalian circannual pacemaker responsible for regulating the seasonal pattern of prolactin has been recently described in sheep. This pacemaker resides within the pars tuberalis, an area of the pituitary gland that densely expresses melatonin receptors. However, the chemical identity of the cell type which acts as the pacemaker remains elusive. Mathematical-modelling approaches have established that this cell must be responsive to the static melatonin signal as well as prolactin negative feedback. Considering that in sheep the gonadotroph is the only cell in the pars tuberalis which expresses the prolactin receptor, and that in other photoperiodic species the thyrotroph is the only cell expressing the melatonin receptor in this tissue, a cell type which expresses both proteins would fulfil the theoretical criteria of a circannual pacemaker. METHODS: Pituitary glands were obtained from female sheep under short days (breeding season) and long days (non-breeding season) and double immunofluorescent staining was conducted to determine the prevalence of bi-hormonal cells in the pars distalis and pars tuberalis using specific antibodies to luteinising hormone-beta and thyroid-stimulating hormone-beta. RESULTS: The results reveal that whilst such a bihormonal cell is clearly present in the pars distalis and constitute 4% of the gonadotroph population in this region, the same cell type is completely absent from the pars tuberalis even though LH gonadotrophs are abundantly expressed. CONCLUSIONS: Based on these findings, together with existing data, we are able to propose an alternative model where the gonadotroph itself is controlled indirectly by neighbouring melatonin responsive cells, allowing it to act as a pacemaker.

Original publication




Journal article



Publication Date





355 - 362


Animals Female Gonadotrophs/metabolism Luteinizing Hormone/*metabolism Melatonin/*metabolism Photoperiod Pituitary Gland, Anterior/cytology/*metabolism Prolactin/metabolism *Seasons Sheep Thyrotropin/*metabolism