Tissue-specific changes in molecular clocks during the transition from pregnancy to lactation in mice.
Circadian clocks regulate homeostasis and mediate responses to stressors. Lactation is one of the most energetically demanding periods of an adult female's life. Peripartum changes occur in almost every organ so the dam can support neonatal growth through milk production while homeostasis is maintained. How circadian clocks are involved in adaptation to lactation is currently unknown. The abundance and temporal pattern of core clock genes' expression were measured in suprachiasmatic nucleus, liver, and mammary from late pregnant and early lactation mice. Tissue-specific changes in molecular clocks occurred between physiological states. Amplitude and robustness of rhythms increased in suprachiasmatic nucleus and liver. Mammary rhythms of core molecular clock genes were suppressed. Attenuated rhythms appeared to be a physiological adaptation of mammary to lactation, because manipulation of timing of suckling resulting in significant differences in plasma prolactin and corticosterone had no effect on amplitude. Analysis of core clock proteins revealed that the stoichiometric relationship between positive (CLOCK) and negative (PER2) components remained 1:1 in liver but was increased to 4:1 in mammary during physiological transition. Induction of differentiation of mammary epithelial cell line HC11 with dexamethasone, insulin, and prolactin resulted in similar stoichiometric changes among positive and negative clock regulators, and prolactin induced phase shifts in HC11 Arntl expression rhythm. Data support that distinct mechanisms drive periparturient changes in mammary clock. Stoichiometric change in clock regulators occurs with gland differentiation. Suppression of mammary clock gene expression rhythms represents a physiological adaptation to suckling cues. Adaptations in mammary clock are likely needed in part to support suckling demands of neonates.
Department of Animal Science, Purdue University, West Lafayette, Indiana theresa-casey@purdue.edu.
Theresa M
TM
Casey
Department of Animal Science, Purdue University, West Lafayette, Indiana.
Jennifer
J
Crodian
Department of Animal Science, Purdue University, West Lafayette, Indiana.
Emily
E
Erickson
Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, New York.
Karen K
KK
Kuropatwinski
Cleveland BioLabs, Buffalo, New York.
Anatoli S
AS
Gleiberman
Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, New York.
Marina P
MP
Antoch
D056930:ARNTL Transcription Factors / Q000378:metabolism; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D002460:Cell Line; D002940:Circadian Rhythm / Q000502:physiology*; D056925:Circadian Rhythm Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D056931:Cryptochromes / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology; D005260:Female; D007774:Lactation / Q000502:physiology*; D008099:Liver / Q000378:metabolism; D008297:Male; D008321:Mammary Glands, Animal / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008892:Milk / Q000737:chemistry; D009419:Nerve Tissue Proteins / Q000378:metabolism; D056950:Period Circadian Proteins / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D013493:Suprachiasmatic Nucleus / Q000378:metabolism
D056930:ARNTL Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D056925:Circadian Rhythm Signaling Peptides and Proteins; D056931:Cryptochromes; D009419:Nerve Tissue Proteins; D056950:Period Circadian Proteins; C538961:Bmal1 protein, mouse; C538964:Cry1 protein, mouse; C538967:Cry2 protein, mouse; C491259:Npas2 protein, mouse; C539023:Per1 protein, mouse; C513312:Per2 protein, mouse; C512645:Per3 protein, mouse
SCN; circadian clock; lactation; liver; mammary; pregnancy; prolactin