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 α and β subtypes of oestrogen receptors (ERα and ERβ) in the mouse SCN. We found that relatively few neurones in the SCN are immunoreactive (IR) for ERα (approximately 4.5% in females and 3% in males), but five- to six-fold more SCN neurones express ERβ. 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 24h substantially reduced the number of ERβ-IR neurones, but not ERα-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 ERα-IR neurones. A higher proportion (approximately 38%) of ERβ-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 ERα and ERβ in various cell populations of the SCN suggest multiple modes of oestrogen signalling within this nucleus, which may modulate circadian functions.
- Vasoactive intestinal polypeptide
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Endocrine and Autonomic Systems
- Cellular and Molecular Neuroscience