Abstracts

RATIONALE: During development, gonadal hormones are important regulators of the sexual differentiation of the central nervous system. Their activity results in permanent morphological and behavioral differences between males and females. Functional sex- and age- differences have been described for the GABA(A)-ergic circuits of the rat substantia nigra pars reticulata (SNR) involved in the control of flurothyl seizures. The presence or absence of testosterone postnatally is a key factor in the functional differentiation of the SNR. To assess whether the effects of testosterone could be mediated via the estrogen receptors (ERs) we studied the ontogeny of ERs-immunoreactive cells in the substantia nigra (SN) of male and female rats.
METHODS: We perfused male and female rats at the following postnatal days (PN) 0, 1, 15, and 30. Adjacent 40 [mu]m sagittal sections were immunostained using a rabbit anti-ER[beta] polyclonal antibody and a mouse anti-ER[alpha] monoclonal antibody. We compared the distribution, intracellular localization, and signal intensity of the ER-positive SNR cells in the various age and sex groups.
RESULTS: ER labeling is present in the soma and in the processes of the SNR cells of both sexes. ER[alpha] positive cells appear earlier in males (PN0) compared to females. At birth, both sexes express ER[beta]. At PN15, there is a peak of ER expression in both sexes. The signal intensity of ER[alpha] however is higher in PN15 males than in females, but ER[beta] is expressed at similar levels in both sexes. At PN30, there is a considerable reduction of ER staining in both sexes. At this age, ER[alpha] staining is present only in the cell soma, and the signal intensity is higher in females compared to males. There are no sex differences in the level of expression of ER[beta] in PN30 rats.
CONCLUSIONS: These data indicate that in the rat SNR: (1) ER-positive cells are present in the SNR of both sexes but the expression pattern changes during distinct developmental periods. (2) ER[alpha] is present earlier in males than in females. (3) Male rats have higher cellular levels of ER[alpha] compared to female rats in the early postnatal period (PN0 [ndash] PN15). (4) The prepubertal downregulation of ER[alpha] protein is sex- dependent (more pronounced in males). (5) During development, there are no sex differences in the expression of ER[beta]. The pattern of ER expression may be one of the factors responsible for the development of the sexual and regional organization of the SNR.
Support: EFA, IRFMN, NIH-NINDS NS20253 and NS30387.