Ontogeny of the androgen receptor in the hippocampus of the Sprague-Dawley rat

Babstock, D.M. (1999) Ontogeny of the androgen receptor in the hippocampus of the Sprague-Dawley rat. Doctoral (PhD) thesis, Memorial University of Newfoundland.

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Abstract

Immunocytochemistry (ICC) with a polyclonal antibody (PG-21) was used to investigate the ontogeny of the androgen receptor (AR) in the hippocampus of Sprague-Dawley rats. Brains of five male and female littermates were examined at each age covering the neonatal (PND 2, 5, 7), juvenile (PND 14), prepubertal (PND 25), and pubertal (PND 40) period with one male and female examined at PND 60. As well, two sets of PND 7 and PND 25 male and female littermates were injected 30 minutes before perfusion with dihydrotestosterone benzoate (DHTB) to look for a possible ligand-dependent increase in staining. The density of staining in the hippocampal CA1, CA3 and DG cell layers was determined in each section with the density of the DG subtracted from the density of the pyramidal cell layers as a control for background staining. -- In the hippocampus of both sexes, AR staining density is described by an inverted U-shaped function between the ages of PND 2 and PND 25 with a peak at PND 7. AR staining density in the CA1 cell layer is at its highest density in both sexes during puberty (PND 40), with significantly greater density in the male. In contrast, at PND 40, AR staining density remains low in the CA3 cell layer. The only other age that exhibits a possible sex difference is PND 7 with a trend within the CA1 cell layer for greater AR staining density in the male. -- In the neonatal and prepubertal animal, the AR staining is dispersed equally throughout the cell with nuclear enhanced density observed at PND 40. The effect of DHTB treatment on AR density depends on age. Increased staining is observed in both sexes at PND 7 whereas, in the prepubertal animals (PND 25), DHTB appears to decrease AR density in females with no consistent effect in males. -- The ontogeny of the AR within the hippocampus is compared to the ontogeny of the AR in other brain areas and to the ontogeny of the estrogen receptor (ER). It is concluded that neonatal and prepubertal hippocampal AR may be regulated by factors other than circulating androgen as AR density is not clearly related to serum testosterone (T) levels and DHTB-treatment does not elicit a nuclear translocation as demonstrated in adult animals. Instead, the AR is equally dispersed throughout the cell, regardless of androgen treatment. Thus, the neonatal and adult AR may be differently regulated and may have different functions. -- Key words: Androgen receptor (AR); immunocytochemistry (ICC); PG-21; ontogeny; hippocampus; CA1; CA3; dihydrotestosterone benzoate (DHTB).

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