Effects of gonadal steroids during pubertal development on androgen and estrogen receptor-alpha immunoreactivity in the hypothalamus and amygdala.

Perinatal development is often viewed as the major window of time for organization of steroid-sensitive neural circuits by steroid hormones. Behavioral and neuroendocrine responses to steroids are dramatically different before and after puberty, suggesting that puberty is another window of time during which gonadal steroids affect neural development. In the present study, we investigated whether the presence of gonadal hormones during pubertal development affects the number of androgen receptor and estrogen receptor alpha-immunoreactive (AR-ir and ER alpha-ir, respectively) cells in limbic regions. Male Syrian hamsters were castrated either before or after pubertal development, and 4 weeks later they received a single injection of testosterone or oil vehicle 4 h prior to tissue collection. Immunocytochemistry for AR and ER alpha was performed on brain sections from testosterone-treated and oil-treated males, respectively. Adult males that had been castrated before puberty had a greater number of AR-ir cells in the medial preoptic nucleus than adult males that had been castrated after puberty. There were no significant differences in ER alpha-ir cell number in any of the brain regions examined. The demonstration that exposure to gonadal hormones during pubertal development is associated with reduced AR-ir in the medial preoptic nucleus indicates that puberty is a period of neural development during which hormones shape steroid-sensitive neural circuits.

Estrogen receptor immunoreactivity in prepubertal and adult male Syrian hamsters.

Estrogen and estrogen receptors (ER) are involved in the expression of steroid-dependent male sexual behavior and negative feedback regulation of the hypothalamic-pituitary-gonadal axis. The purpose of the present experiment was to determine whether there are pubertal changes in ER expression in brain that are correlated with pubertal changes in responsiveness to steroid negative feedback and behavioral activation. We found equivalent numbers of ER-immunoreactive (ER-ir) cells in castrated prepubertal and adult male hamsters in nuclei that comprise the neural circuit that mediate male sexual behavior. Therefore, increases in the number of cells in these nuclei that express ER are not correlated with the increased behavioral responsiveness to steroid hormone shown by hamsters after puberty. The number of ER-ir cells in the ventral medial hypothalamus was less in adults compared with juveniles. This pubertal decrease in ER expression is correlated with the decreased responsiveness to steroid negative feedback in the adult.

Regulation of vascular prostaglandin synthesis by metabolites of arachidonic acid in perfused rabbit aorta.

To address the hypothesis that metabolites of arachidonic acid are important regulators of prostaglandin (PG) synthesis in intact vascular tissue, we studied arachidonate metabolism in rabbit aortas in response to a continuous infusion of arachidonic acid, 10 micrograms/ml. Prostacyclin (PGI2; measured as 6-keto-PGF1 alpha) production rate accelerated during the first 2 min, reached peak velocity at 2 min, and then progressively decelerated. The velocity profile of PGI2 production was similar to that previously reported for cyclooxygenase holoenzyme assayed in vitro, and was consistent with progressive inactivation of the enzymes leading to PGI2 synthesis. We determined the specific inhibition of cyclooxygenase and prostacyclin synthetase by measuring PGI2 and PGE2 production rates and by infusing cyclic endoperoxides. Our results indicate preferential inactivation of cyclooxygenase during arachidonate metabolism, most likely due to cyclooxygenase-derived oxidative intermediates. This was a dose-dependent response and resulted in a progressive decrease in the 6-keto-PGF1 alpha/PGE2 ratio. Exogenously added 15-hydroperoxy eicosatetraenoic acid, on the other hand, actually stimulated cyclooxygenase activity at low doses, while markedly inhibiting prostacyclin synthetase. This finding, along with the accelerating nature of arachidonate metabolism, is consistent with the concept of "peroxide tone" as a mediator of cyclooxygenase activity in this system. These results demonstrate that arachidonate metabolites regulate PG synthesis in intact blood vessels. The progressive enzymatic inhibition intrinsic to arachidonate metabolism may be a model for similar changes occurring in states of enhanced lipid peroxidation. These metabolic alterations might greatly influence the numerous vascular functions known to involve arachidonic acid metabolism.