Clock genes and the long-term regulation of prolactin secretion: Evidence for a photoperiod/circannual timer in the pars tuberalis

G A Lincoln, H Andersson, D Hazlerigg

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

Prolactin secretion is regulated by photoperiod through changes in the 24-h melatonin profile and displays circannual rhythmicity under constant photoperiod. These two processes appear to occur principally within the pituitary gland, controlled by the pars tuberalis. This is evident because: (i) hypothalamic-pituitary disconnected (HPD) sheep show marked changes in prolactin secretion in response to switches in photoperiod and manipulations of melatonin, similar to brain-intact controls; (ii) HPD sheep also show photoperiod-specific, long-term cycles in prolactin secretion under constant long or short days, with the timing maintained even when prolactin secretion is blocked for 2-3 months; and (iii) pars tuberalis cells, but not lactotrophs, express high concentrations of melatonin (MT1) receptor, and exhibit a duration-sensitive, cAMP-dependant, inhibitory response to physiological concentrations of melatonin. This suggests the existence of an intrinsic, reversible photoperiod-circannual timer in pars tuberalis cells. A full complement of clock genes (Bmal1 , Clock , Per1 , Per2 , Cry1 and Cry2) are expressed in the ovine pars tuberalis, and undergo 24-h cyclical expression as observed in a cell autonomous, circadian clock. Activation of Per genes occurs in the early day (melatonin off-set), while activation of Cry genes occurs in the early night (melatonin on-set). This temporal association is evident under both long and short days, thus the Per -Cry interval varies directly with photoperiod. Because, PER : CRY, protein : protein interactions affect stability, nuclear entry and gene transcription based on rodent data, the change in phasing of Per /Cry expression provides a potential mechanism for decoding the long day/short day melatonin signal. A speculative, but testable, extension of this hypothesis is that intrinsically regulated changes in the phase of Per /Cry rhythms, regulates both photorefractoriness and the generation of circannual rhythms in prolactin secretion.

Original languageEnglish
Pages (from-to)390-397
Number of pages8
JournalJournal of Neuroendocrinology
Volume15
Publication statusPublished - 2003

Keywords

  • clock genes
  • melatonin
  • pituitary gland
  • season
  • LUTEINIZING-HORMONE SECRETION
  • DECODING PHOTOPERIODIC TIME
  • PITUITARY-GLAND
  • SYRIAN-HAMSTER
  • SUPRACHIASMATIC NUCLEUS
  • MELATONIN RECEPTORS
  • INDUCED CYCLES
  • EXPRESSION
  • RAMS
  • SHEEP

Cite this

Clock genes and the long-term regulation of prolactin secretion: Evidence for a photoperiod/circannual timer in the pars tuberalis. / Lincoln, G A ; Andersson, H ; Hazlerigg, D .

In: Journal of Neuroendocrinology, Vol. 15, 2003, p. 390-397.

Research output: Contribution to journalArticle

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AB - Prolactin secretion is regulated by photoperiod through changes in the 24-h melatonin profile and displays circannual rhythmicity under constant photoperiod. These two processes appear to occur principally within the pituitary gland, controlled by the pars tuberalis. This is evident because: (i) hypothalamic-pituitary disconnected (HPD) sheep show marked changes in prolactin secretion in response to switches in photoperiod and manipulations of melatonin, similar to brain-intact controls; (ii) HPD sheep also show photoperiod-specific, long-term cycles in prolactin secretion under constant long or short days, with the timing maintained even when prolactin secretion is blocked for 2-3 months; and (iii) pars tuberalis cells, but not lactotrophs, express high concentrations of melatonin (MT1) receptor, and exhibit a duration-sensitive, cAMP-dependant, inhibitory response to physiological concentrations of melatonin. This suggests the existence of an intrinsic, reversible photoperiod-circannual timer in pars tuberalis cells. A full complement of clock genes (Bmal1 , Clock , Per1 , Per2 , Cry1 and Cry2) are expressed in the ovine pars tuberalis, and undergo 24-h cyclical expression as observed in a cell autonomous, circadian clock. Activation of Per genes occurs in the early day (melatonin off-set), while activation of Cry genes occurs in the early night (melatonin on-set). This temporal association is evident under both long and short days, thus the Per -Cry interval varies directly with photoperiod. Because, PER : CRY, protein : protein interactions affect stability, nuclear entry and gene transcription based on rodent data, the change in phasing of Per /Cry expression provides a potential mechanism for decoding the long day/short day melatonin signal. A speculative, but testable, extension of this hypothesis is that intrinsically regulated changes in the phase of Per /Cry rhythms, regulates both photorefractoriness and the generation of circannual rhythms in prolactin secretion.

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