Journal
JOURNAL OF NEUROENDOCRINOLOGY
Volume 20, Issue 11, Pages 1270-1277Publisher
WILEY
DOI: 10.1111/j.1365-2826.2008.01787.x
Keywords
circadian; vasopressin; vasoactive intestinal polypeptide; calbindin; calretinin; oestrogen
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Funding
- National Science Foundation of Hungary [OTKA T46574, OTKA K69127, T73002, NKFP 1A/002/2004]
- European Union [LSHM-CT-2003-50304]
- Wellcome Trust [060202]
- BBSRC [BBD5231861]
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Oestrogen regulates various aspects of circadian rhythm physiology. The presence of oestrogen receptors within the suprachiasmatic nucleus (SCN), the principal circadian oscillator, indicates that some actions of oestrogen on circadian functions may be exerted at that site. The present study analysed sex differences, topographic distribution, and neurochemical phenotype of neurones expressing the alpha and beta subtypes of oestrogen receptors (ER alpha and ER beta) in the mouse SCN. We found that relatively few neurones in the SCN are immunoreactive (IR) for ER alpha (approximately 4.5% in females and 3% in males), but five- to six-fold more SCN neurones express ER beta. ER-IR neurones are primarily in the shell subdivision of the nucleus and show differences between the sexes, significantly greater numbers being found in females. Treatment of male or female gonadectomised mice with oestradiol benzoate for 24 h substantially reduced the number of ER beta-IR neurones, but not ER alpha-IR neurones. Double-labelling immunocytochemical experiments to characterise the phenotype of the oestrogen-receptive neurones showed the presence of the calcium-binding proteins calretinin or calbindin D28K in approximately 12% and 10%, respectively, of ER alpha-IR neurones. A higher proportion (approximately 38%) of ER beta-IR neurones contains calbindin D28K; a few (approximately 2%) express calretinin or vasopressin. These double-labelled cells appear primarily in the shell subdivision of the SCN. Neither vasoactive intestinal polypeptide- nor gastrin releasing peptide-immunoreactivity was observed in ER-IR neurones. These data indicate that the primary target cells for oestrogen are in the shell subdivision of the nucleus. The sexually differentiated expression and distribution of ER alpha and ER beta in various cell populations of the SCN suggest multiple modes of oestrogen signalling within this nucleus, which may modulate circadian functions.
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