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New insights into steroid hormone regulation of progesterone receptor expression: Age, sex and region predict estradiol action in the rat brain
Progesterone receptor expression (PR) is regulated by estradiol in most regions of the adult and developing hypothalamus. The ventromedial nucleus (VMN) of the developing female rat appears to be the exception; PR is present in the absence of circulating gonadal hormones. In the present thesis, the circumstances governing this exception in steroid hormone regulation were explored. Sex, developmental and regional differences in the hormone regulation of PR were revealed. A battery of classic endocrine manipulations revealed that PR in the prenatal VMN was not affected by changes in hormone exposure. However, hormonal regulation of PR in the postnatal VMN was sexually dimorphic. In the neonatal VMN, gonadal hormones regulate PR in the male, but not in the female. Conversely, at a later postnatal age, PR becomes independent of testicular hormones, but is partially dependent on ovarian hormones. In contrast, these endocrine manipulations predictably altered PR within the developing MPN of both males and females, demonstrating a regional difference in estradiol-regulation of PR. In addition, the dependence of PR on estradiol is developmentally regulated. Estradiol induced PR in the adult female but did not affect PR in postnatal female VMN. Ontogenetic analysis revealed that estradiol could not induce PR in the postnatal VMN until around postnatal day 35. The transcription factor islet-1can interfere with the transcriptional function of estrogen receptors (ER), suggesting that Islet-1 may contribute to the sex-, age- and regional differences in estradiol regulation of PR. Levels of Islet-1 were significantly higher in the VMN of neonatal females than in adult females and neonatal males, consistent with the idea that Islet-1 could be obstructing the function of ER to a greater extent in the neonatal female VMN compared to the VMN of adult females and neonatal males. There were no age or sex differences in Islet-1 expression in the MPN. In the developing VMN, PR may not simply be dictated by the presence or absence of estradiol. On the contrary, factors such as Islet-1 may act to modify estrogen regulated gene transcription within the brain in age, sex and region specific ways.
Quadros, Princy Susan, "New insights into steroid hormone regulation of progesterone receptor expression: Age, sex and region predict estradiol action in the rat brain" (2004). Doctoral Dissertations Available from Proquest. AAI3136767.